Surrogate markers of tumoral angiogenesis

BACKGROUND: Angiogenesis is a prerequisite for tumor growth and metastasis. Vascular cell adhesion molecule1 (VCAM-1) is expressed on endothelial cells as a result of vascular endothelial growth factor (VEGF) stimulation. PURPOSE: To determine if measurement in serum of VEGF or VCAM-1 provides an accurate measure of tumor angiogenesis. METHODS: VCAM-1 and VEGF were measured in the serum of women with early and advanced breast cancer by ELISA. Levels were compared to levels of VCAM-1 and VEGF in women with normal breasts and levels of the endothelial glycoprotein von Willebrand factor. Levels of VEGF and VCAM-1 in women with early breast cancer were correlated with established clinicopathological prognostic markers and intratumoral microvessel density (IMD). RESULTS: In early breast cancer serum VCAM-1 correlated closely with the microvessel density in tumors (r=0.61, p<0.001). Women with lymph node-positive and high-grade tumors had higher levels of serum VCAM-1 than women with lymph node-negative and low-grade tumors. Serum VEGF demonstrated no correlation with established prognostic features or IMD. Levels of VCAM-1 and VEGF were raised in women with advanced breast cancer. CONCLUSION: Serum VCAM-1 is a surrogate marker of angiogenesis in breast cancer and its measurement may help in the assessment of antiangiogenic drugs currently in phase II trials.     

Quantitation of angiogenesis and its correlation with vascular endothelial growth factor expression in astrocytic tumors

OBJECTIVE: To quantitate tumor angiogenesis by establishing intratumoral microvessel density (IMD), to study vascular endothelial growth factor (VEGF) expression in different grades of astrocytomas and to correlate VEGF expression with tumor angiogenesis. STUDY DESIGN: Forty cases of astrocytic neoplasms (10 of each grade) were assessed for tumor angiogenesis and VEGF expression. The panendothelial marker CD31 was used to highlight microvessels. Tumor angiogenesis was quantitated as IMD count per square millimeter in areas of high vascularity, or "hot spots," using an image analyzer. VEGF expression was studied in sections of the tumors. IMD counts per square millimeter and VEGF expression were correlated with histologic grade. The angiogenic potential of tumors as reflected by IMD counts per square millimeter was correlated with the intensity of VEGF expression. RESULTS: Vascular proliferation in high grade gliomas was significantly higher as compared to that in low grade gliomas. IMD count per square millimeter revealed a positive correlation with histologic grade in high grade gliomas. Pilocytic astrocytoma and low grade astrocytoma as a group had comparable IMD counts per square millimeter. VEGF expression paralleled IMD counts in rare high grade gliomas only. CONCLUSION: Malignant progression in astrocytoma is heralded and accompanied by increased angiogenesis. VEGF is an important angiogenic factor in high grade gliomas since its expression parallels the increased IMD counts in these tumors. In contrast, in low grade gliomas, angiogenic factors other than VEGF may contribute to vascular proliferation. The results emphasize the role of antiangiogenic therapy as an optimal tool in therapeutic strategies as they become available.     

瘦素及其受体在宫颈癌中的表达和意义

目的探讨瘦素(leptin)及其受体(OB-R)在宫颈癌中的表达与临床病理参数的关系。方法采用免疫组织化学技术检测10例慢性宫颈炎、12例宫颈上皮内瘤样病变、50例宫颈癌中leptin和OB-R的表达,利用CD34标记宫颈癌血管内皮细胞并计算微血管密度(MVD)。结果leptin和OB-R仅在10例慢性宫颈炎、12例上皮内瘤样病变的鳞状上皮层中呈弱阳性表达;50例宫颈癌中Leptin染色( )39例,OB-R染色( )33例;宫颈癌中leptin表达、MVD与肿瘤分化程度、浸润深度和是否远处转移呈正相关(P<0.05),与患者年龄和肿瘤组织学分型无关(P>0.05);OB-R表达与浸润深度和是否远处转移呈正相关(P<0.05),与患者年龄、肿瘤分化程度和组织学分型无关(P>0.05);leptin或OB-R染色( )MVD明显高于染色(-)者。结论Leptin是宫颈癌重要的血管生长因子,瘦素及其受体和MVD与肿瘤的恶性程度密切相关。     

The Role of Respiratory Microbiota in Lung Cancer

Recently, the impact of microorganisms on tumor growth and metastasis has attracted great attention. The pathogenesis and progression of lung cancer are related to an increase in respiratory bacterial load as well as changes in the bacterial community because the microbiota affects tumors in many ways, including canceration, metastasis, angiogenesis, and treatment. The microbiota may increase tumor susceptibility by altering metabolism and immune responses, promoting inflammation, and increasing toxic effects. The microbiota can regulate tumor metastasis by altering multiple cell signaling pathways and participate in tumor angiogenesis through vascular endothelial growth factors (VEGF), endothelial cells (ECs), inflammatory factors and inflammatory cells. Tumor angiogenesis not only maintains tumor growth at the primary site but also promotes tumor metastasis and invasion. Therefore, angiogenesis is an important mediator of the interaction between microorganisms and tumors. The microbiota also plays a part in antitumor therapy. Alteration of the microbiota caused by antibiotics can regulate tumor growth and metastasis. Moreover, the microbiota also influences the efficacy and toxicity of tumor immunotherapy and chemotherapy. Finally, the effects of air pollution, a risk factor for lung cancer, on microorganisms and the possible role of respiratory microorganisms in the effects of air pollution on lung cancer are discussed.     

Expression of human apolipoprotein(a) kringles in colon cancer cells suppresses angiogenesis-dependent tumor growth and peritoneal dissemination

BACKGROUND: Anti-angiogenesis therapy has been regarded as a promising treatment of cancer based on the fact that most tumors and their metastasis are angiogenesis-dependent. Gene therapy can potentially expand the horizons of tumor angiogenesis therapy by virtue of its ability to produce high concentrations of therapeutic agents in a local area for a sustained period. The present study was performed to evaluate the therapeutic potential of gene therapy for the treatment of cancer and metastasis. METHODS: The murine colon carcinoma cell line CT26 was manipulated ex vivo to express an anti-angiogenic molecule, LK68, consisting of human apolipoprotein(a) kringle domains, KIV(9)-KIV(10)-KV, using retrovirus-mediated gene transfer. Its effects on colon tumor growth and metastasis were evaluated in experimental animal models established by injecting LK68-expressing and control CT26 cells subcutaneously or into the peritoneal cavity of BALB/c mice, respectively. RESULTS: Expression of LK68 significantly suppressed colon tumor growth in mice, but did not influence the growth of tumor cells in vitro. Immunohistochemical analysis of tumor tissues revealed a significant reduction in microvessel density in LK68-expressing tumors. Thus, the suppression of tumor growth appears to result mainly from inhibition of tumor angiogenesis. This decrease in vessel density is correlated with a notable increase in tumor cell apoptosis in vivo, but has no influence on proliferation. Moreover, expression of LK68 prevents peritoneal dissemination, and consequently improves overall host survival. CONCLUSIONS: These results collectively indicate that a gene therapy strategy using LK68 cDNA is useful for the treatment for both colon tumor growth and peritoneal dissemination.     

In-vivo visualization of tumor microvessel density and response to anti-angiogenic treatment by high resolution MRI in mice

Purpose

Inhibition of angiogenesis has shown clinical success in patients with cancer. Thus, imaging approaches that allow for the identification of angiogenic tumors and the detection of response to anti-angiogenic treatment are of high clinical relevance.

Experimental Design

We established an in vivo magnetic resonance imaging (MRI) approach that allows us to simultaneously image tumor microvessel density and tumor vessel size in a NSCLC model in mice.

Results

Using microvessel density imaging we demonstrated an increase in microvessel density within 8 days after tumor implantation, while tumor vessel size decreased indicating a switch from macro- to microvessels during tumor growth. Moreover, we could monitor in vivo inhibition of angiogenesis induced by the angiogenesis inhibitor PTK787, resulting in a decrease of microvessel density and a slight increase in tumor vessel size.

Conclusions

We present an in vivo imaging approach that allows us to monitor both tumor microvessel density and tumor vessel size in the tumor. Moreover, this approach enables us to assess, early-on, treatment effects on tumor microvessel density as well as on tumor vessel size. Thus, this imaging-based strategy of validating anti-angiogenic treatment effects has high potential in applications to preclinical and clinical trials.     

Angiogenesis as an independent prognostic indicator in node-negative breast cancer

OBJECTIVE: To quantitate tumor angiogenesis in carcinoma of the breast (stage T2N0M0) by computerized image analysis of CD-31-stained histologic sections and, keeping in view the heterogeneity of tumors, to assess which areas of neovascularization provide the best prognostic indicator. STUDY DESIGN: Thirty-six cases of infiltrating duct carcinoma of the breast, stage T2N0M0, with follow-up of five years, were analyzed. All cases had received uniform initial treatment in the form of mastectomy with axillary clearance and radiotherapy. Intratumoral microvessel density (IMD) counts were done on "hot spots" and "non-hot spots" on CD-31-stained sections using computerized image analysis. Angiogenesis was correlated with other variables, such as age, menopausal status, histologic grade and proliferative activity by univariate and multivariate analyses. RESULTS: Hot-spot IMD counts were highly significant independent prognostic markers in univariate and multivariate analyses. Background vascularity of a tumor was of no value in prognosticating. CONCLUSION: In patients with node negative breast carcinoma, IMD counts in hot spots are an independent prognostic factor in disease-free and overall survival and can be used to separate out patients with T2N0M0 stage in need of systemic adjuvant therapy.     

食管鳞癌VEGF—C mRNA和CD31表达及其意义

To investigate the expression of vascular endothelial growth factor-C (VEGF-C) mRNA and CD 31 in esophageal squamous cell carcinoma (ESCC) and its promotion of lymphatic metastasis. The expression of VEGF-C mRNA was examined in 43 ESCC by in situ hybridization. Intratumoral microvessel density (MVD) was assessed by immunostaining endothelial cells, using anti-CD31 antibody. The positive rate of VEGF-C mRNA expression was 41.86%. The average rank of MVD was 76.36 +/- 20.30/mm2. VEGF-C mRNA expression correlated significantly with lymph node metastasis, TNM stage and depth of invasion (p < 0.05 or p < 0.01) in statistic, but not with histological grade (differentiation) (p > 0.05). MVD correlated significantly with lymph node metastasis and TNM stage (p < 0.05) in statistic, but not with depth of invasion and histological grade (differentiation) (p > 0.05). MVD was significant higher in the VEGF-C positive tumors than negative tumors (p < 0.05). The present study indicated that VEGF-C might play a role in lympatic metastasis via lymphangiogenesis and angiogenesis in ESCC.     

A critical role of Gbetagamma in tumorigenesis and metastasis of breast cancer

A growing body of evidence indicates that G protein-coupled receptors (GPCRs) are involved in breast tumor progression and that targeting GPCRs may be a novel adjuvant strategy in cancer treatment. However, due to the redundant role of multiple GPCRs in tumor development, it may be necessary to target a common signaling component downstream of these receptors to achieve maximum efficacy. GPCRs transmit signals through heterotrimeric G proteins composed of Gα and Gβγ subunits. Here we evaluated the role of Gβγ in breast tumor growth and metastasis both in vitro and in vivo. Our data show that blocking Gβγ signaling with Gα(t) or small molecule inhibitors blocked serum-induced breast tumor cell proliferation as well as tumor cell migration induced by various GPCRs in vitro. Moreover, induced expression of Gα(t) in MDA-MB-231 cells inhibited primary tumor formation and retarded growth of existing breast tumors in nude mice. Blocking Gβγ signaling also dramatically reduced the incidence of spontaneous lung metastasis from primary tumors and decreased tumor formation in the experimental lung metastasis model. Additional studies indicate that Gβγ signaling may also play a role in the generation of a tumor microenvironment permissive for tumor progression, because the inhibition of Gβγ signaling attenuated leukocyte infiltration and angiogenesis in primary breast tumors. Taken together, our data demonstrate a critical role of Gβγ signaling in promoting breast tumor growth and metastasis and suggest that targeting Gβγ may represent a novel therapeutic approach for breast cancer.     

IL-10 promotes resistance to apoptosis and metastatic potential in lung tumor cell lines

Treatment of non-small cell lung carcinoma (NSCLC) remains at a disappointingly low success rate. Not only is metastatic spread common in NSCLC, but therapeutic success decreases dramatically once metastases are present. Understanding factors which contribute to poor prognosis in NSCLC is critical for development of more successful therapeutic approaches. Interleukin-10 (IL-10) expression has been shown in several studies to correlate with a poorer prognosis in NSCLC; however, the mechanisms by which IL-10 affects lung tumor growth and metastases are unclear. The goal of this study was to evaluate the effects of tumor-derived IL-10 on the growth and metastasis of lung cancer cells in a murine model. Lewis lung carcinoma cells were stably transfected with the chicken ovalbumin gene (cOVA) as a model tumor antigen (LL43 tumor cells) and subsequently transfected with the murine IL-10 gene (LL43-10 tumor cells). Subcutaneous growth of the LL43 tumor cells was not affected by expression of IL-10. However, LL43-10 tumors had a fourfold increase in tumor microvessel density, as indicated by CD31 staining. Metastatic potential was also increased in IL-10-expressing lung tumor cells, leading to a greater number of tumor cells in lymph nodes draining the primary tumor site. Finally, exposure of Lewis lung tumor cells in vitro to exogenous IL-10 dramatically increased their resistance to UV-induced apoptosis. These results indicate that a primary effect of IL-10 on lung cancer cells may be to increase their metastatic potential by promoting angiogenesis and resistance to apoptosis.     

Study on the characteristics of contrast-enhanced ultrasound and its utility in assessing the microvessel density in ovarian tumors or tumor-like lesions

Angiogenesis is a critical factor in tumor growth and metastasis, and microvessel density (MVD) was an important parameter for assessing vessels in tumors. However, radiologic assessment of tumor vascularity is not yet well established. In our study, we aimed at investigating the efficacy of contrast-enhanced ultrasonography (CEUS) in exploring the vascularity of the ovarian tumors or tumor-like lesions to assess the relationship between the parameters of the peak intensity (PI) and area under curve (AUC) on CEUS and MVD in ovarian masses. Compared to the contrast-enhanced ultrasound technique, conventional ultrasound shows limitation in differentiating benign and malignant ovarian tumors. The former is promising in improving the sensitivity of detecting small vessels and blood flow in ovarian tumors. Our results showed clear differences in enhancement patterns between benign and malignant ovary tumors or tumor-like lesions. The PI and AUC in the malignant tumors were significantly higher than those in the benign tumors or tumor-like lesions (p=0.001 and =0.01, respectively). The MVD was 43.1 ± 20.4 in the benign tumors or tumor-like lesions and was 65.3 ± 22.3 in the malignant ones (p= 0.01). In both the benign and malignant groups, the PI and AUC were correlated significantly with the MVD (r=0.595, p = 0.001; r =0.533, p = 0.003, respectively). The PI and AUC in CEUS can reflect the MVD in ovarin tumors. The PI and AUC of the ovarian masses in the contrast transvaginal sonography show significant correlation with the angiogenesis and may help in assessing tumor vascularity in ovarian masses.     

源于Ⅳ型胶原的肿瘤血管生成抑制剂

新血管生成是各种生理和病理过程发生的基础。在胚胎形成和胎盘发育等正常生理过程中,新血管的生成是至关重要的;然而对于一些疾病的产生,特别是肿瘤的生长、进展和转移,同样离不开血管生成的作用。伴随着“抗肿瘤血管生成疗法”的提出,控制血管生成“开关”的血管生成刺激因子和抑制因子成为研究的热点。Arresten、Canstatin、Tumstatin和Hexastatin是近些年发现的内源性的血管生成抑制因子,它们同系Ⅳ型胶原α链的非胶原区NC1,具有相似的结构和分子量大小,现有研究表明,它们能与内皮细胞表面整合素受体相结合,有效地抑制内皮细胞的增殖和迁移,降低肿瘤组织的微血管密度,切断肿瘤的营养和氧气供给,从而抑制肿瘤的生长和转移。对其作用机制的研究,将有助于肿瘤血管生成抑制剂新药的研发。     

Inhibition of osteopontin would suppress angiogenesis in gastric cancer.

Osteopontin (OPN) plays an important role in tumorigenesis, tumor invasion, and metastasis in many types of cancers, including gastric cancer. Recently, much interest has been focused on the role of OPN in tumor angiogenesis. Our previous studies have shown that OPN is overexpressed, and associated with mean microvessel density in, the tissue samples of patients with gastric cancer. In the present study, we aimed to further determine and provide evidence for the role of OPN in gastric-cancer-associated angiogenesis by diminishing OPN expression in gastric cancer cells using the small interference RNA method, and then evaluate the effects of OPN on gastric cancer-associated angiogenesis by in vivo and in vitro assays. Our results revealed that reduced OPN production by gastric cancer cells would reduce the proliferation, migration, and tube formation of human umbilical vein endothelial cells, and lead to a lower microvessel density, i.e., angiogenesis, in transplanted tumors of mice. These data confirm the positive role of OPN in gastric-cancer-associated angiogenesis.     

Significance of soluble endothelial molecule E-selectin in patients with breast cancer

Increasing evidence suggests that endothelial cells are involved in tumor growth and metastasis. E-selectin, an adhesion molecule specifically expressed or secreted by activated endothelial cells, may enhance tumor angiogenesis and the adhesion of tumor cells to endothelial cells at distant sites. The aim of this study was to assess the relationship between concentrations of circulating soluble E-selectin and clinical, pathological and biological features in patients with breast cancer (BC). sE-selectin concentrations were analyzed by an ELISA method in sera from 113 patients with metastatic BC, 30 patients with primary inflammatory BC, 105 patients with primary non-inflammatory BC, 456 patients with node-negative BC, and 42 healthy controls. sE-selectin in the metastatic BC group was significantly higher than in the healthy control group. In metastatic BC, sE-selectin was significantly higher in patients with liver metastases than in patients without liver metastases. In patients with primary non-inflammatory BC, a negative correlation was found between sE-selectin concentrations and tumoral microvessel count. In overall and disease-free survival studies performed in the node-negative population (median follow-up duration 7.5 years), multivariate analyses demonstrated a prognostic value of sE-selectin and tumor size. This study suggests that endothelial activation might play a role in the development of BC. This role seems not to be related to angiogenesis.     

Forced expression of MMP9 rescues the loss of angiogenesis and abrogates metastasis of pancreatic tumors triggered by the absence of host SPARC

Pancreatic adenocarcinoma is characterized by desmoplasia, local invasion, and metastasis. These features are regulated in part by MMP9 and SPARC. To explore the interaction of SPARC and MMP9 in cancer, we first established orthotopic pancreatic tumors in SPARC-null and wild-type mice with the murine pancreatic adenocarcinoma cell line, PAN02. MMP9 expression was higher in tumors from wild-type compared to SPARC-null mice. Coincident with lower MMP9 expression, tumors grown in SPARC-null mice were significantly larger, had decreased ECM deposition and reduced microvessel density compared to wild-type controls. In addition, metastasis was enhanced in the absence of host SPARC. Therefore, we next analyzed the orthotopic tumor growth of PAN02 cells transduced with MMP9 or a control empty vector. Forced expression of MMP9 by the PAN02 cells resulted in larger tumors in both wild-type and SPARC-null animals compared to empty vector controls and further diminished ECM deposition. Importantly, forced expression of MMP9 within the tumor reversed the decrease in angiogenesis and abrogated the metastatic potential displayed by control tumors grown in SPARC-null mice. Finally, contrary to the in vivo results, MMP9 increased cell migration in vitro, which was blocked by the addition of SPARC. These results suggest that SPARC and MMP9 interact to regulate many stages of tumor progression including ECM deposition, angiogenesis and metastasis.     

Apolipoprotein(a), a link between atherosclerosis and tumor angiogenesis

Lipoprotein (a) [Lp(a)] is a LDL-like particle with one apolipoprotein(a) [apo(a)] covalently bound to apolipoprotein B, the structural protein of Low Density Lipoprotein (LDL). Lewis Lung Carcinoma (LL/2) cells exhibited delayed growth and reduced angiogenesis in apo(a) transgenic mice, expressing a recombinant apo(a) [r-apo(a)] with 18 kringle 4 repeats. The mean microvessel density of subcutaneous LL/2 tumors from apo(a) transgenic mice was significantly lower than that of tumors from control wild type mice. CHO cells secreting a truncated apo(a) protein with only six kringle 4 repeats did not exhibit delayed tumor growth nor did it impair angiogenesis. These data point to an unappreciated role of human apo(a) in angiogenesis and cancer biology. As angiogenesis is necessary for reendothelialization following vascular injury, suppression of angiogenesis by apo(a) may also contribute to the atherogenicity of apo(a). The differences between the truncated apo(a) and r-apo(a) are consistent with the higher atherogenicity of higher molecular weight isoforms.     

不同剂量的塞来昔布对C57BL/6小鼠移植瘤微淋巴管密度抑制作用的研究(英文)

目的:观察不同剂量的塞来昔布对C57BL/6小鼠肺癌移植瘤生长、COX-2表达和微淋巴管密度影响,探讨塞来昔布对C57BL/6小鼠肺癌移植瘤淋巴管生成可能作用机制及量效关系。方法:将Lewis肺癌细胞株接种于C57BL/6小鼠左侧腹股沟皮下建立移植瘤模型,随机分为4组:对照组、塞来昔布低剂量、中剂量、高剂量组。观察荷瘤小鼠生存状态,瘤体积变化,种瘤42天后牺牲小鼠,western blot半定量检测COX-2表达及微淋巴管密度。结果:Western blot半定量显示:塞来昔布高、中剂量组COX-2的表达水平及免疫组织化学染色微淋巴管密度计数均明显减低,差异有统计学意义(P0.05),低剂量组略有减低但差异无统计学意义(P0.05)。抑制程度呈明显的剂量依赖性。结论:塞来昔布抑制Lewis肺癌移植瘤的生长及淋巴转移,可能与下调COX-2的表达,阻遏了淋巴管生成的信号通路,抑制微淋巴管生成有关,该抑制作用呈一定的剂量相关性。     

Expression of periostin in patients with non-small cell lung cancer: correlation with angiogenesis and lymphangiogenesis

The aim of this study was to evaluate periostin expression measured immunohistochemically in patients with non-small cell lung cancer (NSCLC) and to determine its association with clinical features, prognosis, angiogenesis, and lymphangiogenesis. We investigated periostin expression in a series of 88 patients with NSCLC. We also determined whether expression of periostin correlated with microvessel density and lymphatic microvessel density. Periostin was expressed in 42% of 88 patients. Its expression was significantly correlated with tumor size, lymph node metastasis, disease stage, and lymphatic invasion (p=0.0128, 0.0015, 0.0310 and 0.0273, respectively). There also was a significant relation between periostin expression and microvessel density and lymphatic microvessel density (all p<0.0001). Five-year survival rates were better in patients with negative periostin expression than in those with positive periostin expression (p=0.0044). Periostin expression was not significant in a multivariate additive model. Our findings show that periostin correlates with increased tumor progression and a worse prognosis in NSCLC, as well as with angiogenesis and lymphangiogenesis.     

神经节苷脂GD3与肿瘤的血管生成作用(英文)

 血管生成作用 (angiogenesis)是实体瘤 (solidtumor)生长和扩散的必要条件 .实体瘤的微血管密度与肿瘤的恶性程度成正相关 ,而且也与病人的预后密切相关 .因此 ,对抗血管生成作用是一种很有吸引力的肿瘤疗法 .神经节苷脂GD3在多种类型的肿瘤中超常表达 .一般认为 ,神经节苷脂GD3有增强肿瘤本身及邻近组织中的血管生成作用 ,从而促进肿瘤的演进和转移 .最近的研究工作为这一假设提供了有力的实验证据 .应用GD3合酶的反意DNA转染肿瘤细胞从而抑制细胞中的GD3合酶的表达 ,极大地降低了细胞的内源GD3含量 .进一步的研究证明 ,抑制肿瘤细胞的GD3合成明显地降低了该肿瘤细胞的血管内皮生长因子 (VEGF)的水平 ,并使血管生成作用降至最小限度 .这些实验说明GD3在肿瘤的血管生成中具有重要的作用 .此外 ,GD3作为肿瘤的一种相关抗原 ,它与血管生成因子的协同效应将在未来的联合基因疗法中起到重要的作用     

Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes

Development and preclinical testing of new cancer therapies is limited by the scarcity of in vivo models that authentically reproduce tumor growth and metastatic progression. We report new models for breast tumor growth and metastasis in the form of transplantable tumors derived directly from individuals undergoing treatment for breast cancer. These tumor grafts illustrate the diversity of human breast cancer and maintain essential features of the original tumors, including metastasis to specific sites. Co-engraftment of primary human mesenchymal stem cells maintains phenotypic stability of the grafts and increases tumor growth by promoting angiogenesis. We also report that tumor engraftment is a prognostic indicator of disease outcome for women with newly diagnosed breast cancer; orthotopic breast tumor grafting is a step toward individualized models for tumor growth, metastasis and prognosis. This bank of tumor grafts also serves as a publicly available resource for new models in which to study the biology of breast cancer.