共查询到20条相似文献,搜索用时 31 毫秒
1.
Zeru Feng Qiuxuan Yu Ting Zhang Wanpeng Tie Jing Li Xikun Zhou 《Journal of cellular and molecular medicine》2020,24(3):2076-2086
Malignant tumours are one of the major diseases that seriously endanger human health. The characteristics of their invasion and metastasis are one of the main causes of death in cancer patients, and these features cannot be separated from the participation of various molecules‐related cells living in the tumour microenvironment and specific structures. Tumour invasion can approximately be divided into several specific steps according to the movement of tumour cells. In each step, there are different actions in the tumour microenvironment that mediate the interactions among substances. Researchers are attempting to clarify every mechanism of the tumour dissemination. However, there is still a long way to the final determination. Here, we review these interactions in tumour invasion and metastasis at the structural, molecular and cellular levels. We also discuss the ongoing studies and the promise of targeting metastasis in tumour therapy. 相似文献
2.
Klein CA 《Trends in cell biology》2000,10(11):489-493
Despite an increasing molecular-genetic understanding of the development of malignant epithelial neoplasias, the frontline therapy for patients with carcinomas is still surgery. Systemic adjuvant treatments such as chemotherapy or immunotherapy have had limited success perhaps because they are based on analysis of the primary tumour or on cell lines derived from metastasis. However, the characteristics of systemically disseminated tumour cells can be very different from that of the primary tumour or end-stage metastasis. Consequently, there is a need to study the evolution and nature of systemic cancer directly in order to identify new target structures for therapy present on the potential precursors of metastasis--the disseminated tumour cells. 相似文献
3.
Ya Qi Cheng Shou Bi Wang Jia Hui Liu Lin Jin Ying Liu Chao Yang Li Ya Ru Su Yu Run Liu Xuan Sang Qi Wan Chang Liu Liu Yang Zhi Chong Wang 《Cell proliferation》2020,53(8)
The tumour microenvironment (TME) plays a pivotal role in tumour fate determination. The TME acts together with the genetic material of tumour cells to determine their initiation, metastasis and drug resistance. Stromal cells in the TME promote the growth and metastasis of tumour cells by secreting soluble molecules or exosomes. The abnormal microenvironment reduces immune surveillance and tumour killing. The TME causes low anti‐tumour drug penetration and reactivity and high drug resistance. Tumour angiogenesis and microenvironmental hypoxia limit the drug concentration within the TME and enhance the stemness of tumour cells. Therefore, modifying the TME to effectively attack tumour cells could represent a comprehensive and effective anti‐tumour strategy. Normal cells, such as stem cells and immune cells, can penetrate and disrupt the abnormal TME. Reconstruction of the TME with healthy cells is an exciting new direction for tumour treatment. We will elaborate on the mechanism of the TME to support tumours and the current cell therapies for targeting tumours and the TME—such as immune cell therapies, haematopoietic stem cell (HSC) transplantation therapies, mesenchymal stem cell (MSC) transfer and embryonic stem cell‐based microenvironment therapies—to provide novel ideas for producing breakthroughs in tumour therapy strategies. 相似文献
4.
Zhen Bao Wei Zeng Di Zhang Liyong Wang Xin Deng Jianqin Lai Jian Li Jin Gong Guoan Xiang 《International journal of biological sciences》2022,18(7):2867
Background: There is increasing evidence that tumour-associated macrophages (TAMs) are critical in the formation of lung metastases. However, the molecular mechanisms of tumour interactions with TAMs via EMT are largely unknown.Methods: The mechanism of lung metastasis was studied in patient tissues. The mechanism of SNAIL regulation of the interaction between mesenchymal cells and M2 macrophages was elucidated using coculture of M2 macrophages and Transwell assays in vitro and in vivo in nude mice and NOD-SCID mice.Results: We demonstrated for the first time that SNAIL and CXCL2 were abnormally overexpressed in colorectal cancer, especially lung metastasis, and were associated with poor prognosis in colorectal cancer patients. We demonstrated that SNAIL promoted the secretion of CXCL2 by mesenchymal cells and induced the activation of M2 macrophages. We found that CXCL2 attracted M2-type macrophages to infiltrate and promote tumour metastasis.Conclusion: These findings suggest that SNAIL promotes epithelial tumour transformation, and that transformed mesenchymal cells secrete CXCL2, which promotes M2 macrophage infiltration and tumour cell metastasis. These findings elucidate the tumour-TAM interaction in the metastatic microenvironment, which is mediated by tumour-derived CXCL2 and affects lung metastasis. This study also provides a theoretical basis for the occurrence of secondary lung cancer. 相似文献
5.
Tight Junctions govern the permeability of endothelial and epithelial cells and are the most topical structures of these cell types. Tight junctions create an intercellular barrier and intramembrane diffusion fence. An important step in the formation of cancer metastases interaction and penetration of the vascular endothelium by dissociated cancer cells. Early studies demonstrated a correlation between the reduction of tight junctions and tumour differentiation and experimental evidence has emerged to place tight junctions in the frontline as the structure that cancer cells must overcome in order to metastasise. Changes in tight junction function are thus an early and key aspect in cancer metastasis. Further work is required to fully realise the potential that this structure has in cancer invasion and metastasis in order to develop new and novel therapies in the prevention of tumour metastasis. 相似文献
6.
Florian Lang Christos Stournaras 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2014,369(1638)
Ion transport across the cell membrane mediated by channels and carriers participate in the regulation of tumour cell survival, death and motility. Moreover, the altered regulation of channels and carriers is part of neoplastic transformation. Experimental modification of channel and transporter activity impacts tumour cell survival, proliferation, malignant progression, invasive behaviour or therapy resistance of tumour cells. A wide variety of distinct Ca2+ permeable channels, K+ channels, Na+ channels and anion channels have been implicated in tumour growth and metastasis. Further experimental information is, however, needed to define the specific role of individual channel isoforms critically important for malignancy. Compelling experimental evidence supports the assumption that the pharmacological inhibition of ion channels or their regulators may be attractive targets to counteract tumour growth, prevent metastasis and overcome therapy resistance of tumour cells. This short review discusses the role of Ca2+ permeable channels, K+ channels, Na+ channels and anion channels in tumour growth and metastasis and the therapeutic potential of respective inhibitors. 相似文献
7.
Several bone marrow-derived cells have been shown to promote tumour growth and progression. These cells can home to the primary tumour and become active components of the tumour microenvironment. Recent studies have also identified bone marrow-derived cells—such as mesenchymal stem cells and regulatory T cells—as contributors to cancer metastasis. The innate versatility of these cells provides diverse functional aid to promote malignancy, ranging from structural support to signal-mediated suppression of the host immune response. Here, we review the role of mesenchymal stem cells and regulatory T cells in cancer metastasis. A better understanding of the bipolar nature of these bone marrow-derived cells in physiological and malignant contexts could pave the way for new therapeutics against metastatic disease. 相似文献
8.
ABSTRACT: Cancer-initiating cells display aberrant functional and phenotypic characteristics of normal stem cells from which they evolved by accumulation of multiple cytogenetic and/or epigenetic alterations. Signal transduction pathways which are essential for normal stem cell function are abnormally expressed by cancer cells, with a cancer cell phenotype playing an essential role in cancerization and metastasis.Local tumour progression, metastasis and metastatic tumour growth are mediated by direct cell-to-cell and paracrine reciprocal interactions between cancer cells and various stromal cells including fibroblasts, macrophages, bone marrow derived stem cells and progenitor cells. These interactions mediate breakdown of basement membrane barriers and angiogenesis both locally at the invasive front of the primary tumour and at the distant metastatic site; attract primary tumour cells to the candidate metastatic site; and promote proliferation, survival and growth of primary tumour cells and of metastatic cells at their distant site.It is the purpose of this article to highlight the analogies between some of the genetic programs of normal stem cells, and of cancer cells participating in the process of metastasis. 相似文献
9.
Integrin signalling during tumour progression 总被引:18,自引:0,他引:18
During progression from tumour growth to metastasis, specific integrin signals enable cancer cells to detach from neighbouring cells, re-orientate their polarity during migration, and survive and proliferate in foreign microenvironments. There is increasing evidence that certain integrins associate with receptor tyrosine kinases (RTKs) to activate signalling pathways that are necessary for tumour invasion and metastasis. The effect of these integrins might be especially important in cancer cells that have activating mutations, or amplifications, of the genes that encode these RTKs. 相似文献
10.
Glycan changes: cancer metastasis and anti-cancer vaccines 总被引:1,自引:0,他引:1
Complex carbohydrates, which are major components of the cell membrane, perform important functions in cell-cell and cell-extracellular
matrix interactions, as well as in signal transduction. They comprise three kinds of biomolecules: glycoproteins, proteoglycans
and glycosphingolipids. Recent studies have also shown that glycan changes in malignant cells take a variety of forms and
mediate key pathophysiological events during the various stages of tumour progression. Glycosylation changes are universal
hallmarks of malignant transformation and tumour progression in human cancer, which take place on the whole cells or some
specific molecules. Accordingly, those changes make them prominent candidates for cancer biomarkers in the meantime. This
review mainly focuses on the correlation between glycosylation and the metastasis potential of tumour cells from comprehensive
aspects to further address the vital roles of glycans in oncogenesising. Moreover, utilizing these glycosylation changes to
ward off tumour metastasis by means of anti-adhesion approach or devising anti-cancer vaccine is one of promising targets
of future study. 相似文献
11.
Yuanyuan An Fengtian Liu Ying Chen Qing Yang 《Journal of cellular and molecular medicine》2020,24(1):13-24
Multiple studies have shown that cancer‐associated fibroblasts (CAFs) play an important role in tumour progression, including carcinogenesis, invasion, metastasis and the chemoresistance of cancer cells. Immune cells, including macrophages, natural killer cells, dendritic cells and T cells, play a dual role in the tumour microenvironment. Although increasing research has focused on studying interactions between distinct cells in the tumour microenvironment, the complex relationships between CAFs and immune cells remain unclear and need further study. Here, we summarize our current understanding of crosstalk between CAFs and immune cells, which may help clarify their diagnostic and therapeutic value in tumour progression. 相似文献
12.
13.
Inappropriate chemokine/receptor expression or regulation is linked to many diseases, especially those characterized by an excessive cellular infiltrate, such as rheumatoid arthritis and other inflammatory disorders. There is now overwhelming evidence that chemokines are also involved in the progression of cancer, where they function in several capacities. First, specific chemokine-receptor pairs are involved in tumour metastasis. This is not surprising, in view of their role as chemoattractants in cell migration. Secondly, chemokines help to shape the tumour microenvironment, often in favour of tumour growth and metastasis, by recruitment of leucocytes and activation of pro-inflammatory mediators. Emerging evidence suggests that chemokine receptor signalling also contributes to survival and proliferation, which may be particularly important for metastasized cells to adapt to foreign environments. However, there is considerable diversity and complexity in the chemokine network, both at the chemokine/receptor level and in the downstream signalling pathways they couple into, which may be key to a better understanding of how and why particular chemokines contribute to cancer growth and metastasis. Further investigation into these areas may identify targets that, if inhibited, could render cancer cells more susceptible to chemotherapy. 相似文献
14.
Li Zhang Linyu Zhu Xiaohan Yao Xiaohan Lou Jiajia Wan Xixi Duan Longze Pan Anqi Li Zhuoyu Gu Ming Wang Fazhan Wang Zhihai Qin 《International journal of biological sciences》2022,18(4):1476
Chemotherapeutic drugs have been successfully used to treat several cancers, including melanoma. However, metastasis occasionally occurs after chemotherapy. Here, we reported that paclitaxel (PTX) treatment for B16F10 tumour in mice led to an enhanced lymphatic metastasis of the melanoma cells, although a significant inhibition of tumour growth at the injection site was observed. Further study demonstrated that PTX upregulated the expression of C-C chemokine receptor type 7 (CCR7) in B16F10 cells, enhancing their migration through the activation of JNK and p38 signalling pathways. Loss of CCR7 or blockade of C-C motif chemokine ligand 21 (CCL21)/CCR7 axis abolished the pro-migration effect of PTX on B16F10 melanoma cells. Importantly, combination of PTX and CCR7 mAb could simultaneously delay the tumour growth and reduce the lymphatic metastasis in B16F10 melanoma. The blockade of CCL21/CCR7 axis may collectively serve as a strategy for lymphatic metastasis in some melanoma after chemotherapy. 相似文献
15.
Most tumours contain a heterogeneous population of cancer cells, which harbour a range of genetic mutations and have probably undergone deregulated differentiation programmes that allow them to adapt to tumour microenvironments. Another explanation for tumour heterogeneity might be that the cells within a tumour are derived from tumour‐initiating cells through diverse differentiation programmes. Tumour‐initiating cells are thought to constitute one or more distinct subpopulations within a tumour and to drive tumour initiation, development and metastasis, as well as to be responsible for their recurrence after therapy. Recent studies have raised crucial questions about the nature, frequency and importance of melanoma‐initiating cells. Here, we discuss our current understanding of melanoma‐initiating cells and outline several approaches that the scientific community might consider to resolve the controversies surrounding these cells. 相似文献
16.
Kaiwen Zhang Dong Liu Jianmei Zhao Si Shi Xin He Peng Da Yiwen You Bo You 《Cell death & disease》2021,12(6)
Distant metastasis accompanied by angiogenesis is the main cause of nasopharyngeal carcinoma (NPC)-related death. Nuclear exosomes (nEXOs) are potential tumour biomarkers. High mobility group box 3 (HMGB3), a nuclear protein, is known to be overexpressed in cancers. However, its role in NPC has not been elucidated. Here, we explore for the first time the function of nEXO HMGB3 in tumour angiogenesis involved in NPC metastasis using a series of in vitro experiments with NPC cell lines and clinical specimens and in vivo experiments with tumour xenograft zebrafish angiogenesis model. We found a high expression of HMGB3 in NPC, accompanied by the formation of micronuclei, to be associated with metastasis. Furthermore, the NPC-secreted HMGB3 expression was associated with tumour angiogenesis. Moreover, HMGB3-containing nEXOs, derived from the micronuclei of NPC cells, were ingested by the human umbilical vein endothelial cells (HUVECs), and accelerated angiogenesis in vitro and in vivo. Importantly, western blotting and flow cytometry analysis showed that circulating nEXO HMGB3 positively correlated with NPC metastasis. In summary, nEXO HMGB3 can be a significant biomarker of NPC metastasis and provide a novel basis for anti-angiogenesis therapy in clinical metastasis.Subject terms: Metastasis, Tumour angiogenesis 相似文献
17.
The adhesion of tumour cells to the endothelial cells of blood vessels of the microcirculation represents a crucial step in
haematogenous metastasis formation. Similar to leukocyte extravasation, selectins mediate initial tumour cell rolling on endothelium.
An additional mechanism of leukocyte adhesion to endothelial cells is mediated by hyaluronan (HA). However, data on the interaction
of tumour cells with hyaluronan under shear stress are lacking. The expression of the hyaluronan binding protein CD44 on tumour
cell surfaces was evaluated using flow cytometry. The adhesion of tumour cells to HA with regard to adhesive events and rolling
velocity was determined in flow assays in the human small cell lung cancer (SCLC) cell lines SW2, H69, H82, OH1 and OH3, the
colon carcinoma cell line HT29 and the melanoma cell line MeWo. Hyaluronan deposition in human and mouse lung blood vessels
was histochemically determined. MeWo adhered best to HA followed by HT29. SCLC cell lines showed the lowest CD44 expression
on the cell surface and lowest number of adhesive events. While hyaluronan was deposited in patches in the microvasculature
of the alveolar septum in the human lung, it was only present in the periarterial space in the mouse lung. Certain tumour
entities bind to HA under physiological shear stresses so that HA can be considered a further ligand for cell extravasation
in haematogenous metastasis. As hyaluronan is deposited within the pulmonary microvasculature, it may well serve as a ligand
for its binding partner CD44, which is expressed by many tumour cells. 相似文献
18.
Increasing our knowledge of the mechanisms regulating cell proliferation, migration and invasion are central to understanding tumour progression and metastasis. The local tumour microenvironment contributes to the transformed phenotype in cancer by providing specific environmental cues that alter the cells behaviour and promotes metastasis. Fibroblasts have a strong association with cancer and in recent times there has been some emphasis in designing novel therapeutic strategies that alter fibroblast behaviour in the tumour microenvironment. Fibroblasts produce growth factors, chemokines and many of the proteins laid down in the ECM (extracellular matrix) that promote angiogenesis, inflammation and tumour progression. In this study, we use a label-free RTCA (real-time cell analysis) platform (xCELLigence) to investigate how media derived from human fibroblasts alters cancer cell behaviour. We used a series of complimentary and novel experimental approaches to show HCT116 cells adhere, proliferate and migrate significantly faster in the presence of media from human fibroblasts. As well as this, we used the xCELLigence CIM-plates system to show that HCT116 cells invade matrigel layers aggressively when migrating towards media derived from human fibroblasts. These data strongly suggest that fibroblasts have the ability to increase the migratory and invasive properties of HCT116 cells. This is the first study that provides real-time data on fibroblast-mediated migration and invasion kinetics of colon cancer cells. 相似文献
19.
Richter U Schröder C Wicklein D Lange T Geleff S Dippel V Schumacher U Klutmann S 《Histochemistry and cell biology》2011,135(5):499-512
Haematogenous metastasis of small cell lung cancer (SCLC) is still a poorly understood process and represents the life threatening
event in this malignancy. In particular, the rate-limiting step within the metastatic cascade is not yet clearly defined although,
many findings indicate, that extravasation of circulating tumour cells is crucially important as most tumour cells within
the circulation undergo apoptosis. If extravasation of SCLC tumour cells mimics leukocyte–endothelial interactions, SCLC cells
should adhere to E- and P-selectins expressed on the luminal surface of activated endothelium. The adhesion to E- and P-selectin
under physiological shear stress with regard to adhesive events, rolling behaviour and rolling velocity was determined in
the human SCLC cell lines SW2, H69, H82, OH1 and OH3. OH1 SCLC cells adhered best to recombinant human (rh) E-selectin FC-chimeras
and human lung endothelial cells (HPMEC), H82 SCLC cells adhered best to activated human umbilical vein endothelial cells
(HUVEC) under physiological shear stress. As OH1 cells had also produced by far the highest number of spontaneous lung metastases
when xenografted into pfp/rag2 mice in previous experiments our findings implicate that adhesion of SCLC cells to E-selectin
is of paramount importance in SCLC metastasis formation. 相似文献
20.
Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis 总被引:1,自引:0,他引:1
Primary tumours influence the environment in the lungs before metastasis. However, the mechanism of metastasis is not well understood. Here, we show that the inflammatory chemoattractants S100A8 and S100A9, whose expression is induced by distant primary tumours, attract Mac 1 (macrophage antigen 1)(+)-myeloid cells in the premetastatic lung. In addition, tumour cells use this mechanism, through activation of the mitogen-activated protein kinase (MAPK) p38, to acquire migration activity with pseudopodia for invasion (invadopodia). The expression of S100A8 and S100A9 was eliminated in lung Mac 1(+)-myeloid cells and endothelial cells deprived of soluble factors, such as vascular endothelial growth factor A (VEGF-A), tumour necrosis factor alpha (TNFalpha) and transforming growth factor beta (TGFbeta) both in vitro and in vivo. Neutralizing anti-S100A8 and anti-S100A9 antibodies blocked the morphological changes and migration of tumour cells and Mac 1(+)-myeloid cells. Thus, the S100A8 and S100A9 pathway may be common to both myeloid cell recruitment and tumour-cell invasion. 相似文献