Autocrine and paracrine growth regulation of human breast cancer |
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| Authors: | M E Lippman R B Dickson A Kasid E Gelmann N Davidson M McManaway K Huff D Bronzert S Bates S Swain |
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| Institution: | 1. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women''s Hospital and Harvard Medical School, Boston, MA, USA;2. Center for Healthcare Delivery Sciences (C4HDS), Department of Medicine, Brigham and Women''s Hospital and Harvard Medical School, Boston, MA, USA;3. Atrius Health, Newton, MA, USA;4. Western University of Health Sciences, Pomona, CA;5. Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada;6. Division of Rheumatology, Brigham and Women''s Hospital and Harvard Medical School, Boston, MA, USA;7. Division of General Internal Medicine and Department of Health Care Policy, Brigham and Women''s Hospital and Harvard Medical School, Boston, MA, USA;1. Raybiotech, Inc., 3607 Parkway Lane, Norcross, GA, USA;2. RayBiotech, Inc., Guangzhou, No. 79 Ruihe Road, Huangpu District, Guangzhou, China;3. Department of Gynaecologic Oncology, Cancer Institute and Hospital, Guangzhou Medical University, Guangzhou, China;4. Department of Pharmaceutical Sciences, College of Pharmacy and Health Science, St. John''s University, Queens, NY, USA;5. Sun Yat-sen University Cancer Center, Guangzhou, China;6. South China Biochip Research Center, No. 79 Ruihe Road, Huangpu District, Guangzhou, China |
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| Abstract: | Previous work from our laboratory has demonstrated that human breast cancer (BC) cells in culture can be stimulated by physiologic concentrations of estrogen. In an effort to further understand this process, we have examined the biochemical and biological properties of proteins secreted by human BC cells in vitro. We have developed a defined medium system which simultaneously allows the collection of factors secreted by the BC cells, facilitates their purification and allows for an unequivocal assay of their effect on other BC cells. By both biochemical and radioimmunoassay procedures, MCF-7 cells secrete large quantities of IGF-I-like activity. The cells contain receptors for IGF-I and are stimulated by physiologic concentrations of IGF-I. Multiple additional peaks of growth stimulatory activity can be obtained by partial purification of conditioned media from human BC cells by sequential dialysis, acid extraction and Biogel P60 chromatography. These peaks are induced up to 200-fold by physiologic concentrations of estrogen. Several of these peaks cross-react in a radioreceptor assay with EGF and are thus candidates for transforming growth factors. Monoclonal antibodies (MCA) have been prepared which react with secreted proteins from the MCF-7 cells. One of these MCAs binds to material from MCF-7 and ZR-75-1 hormone-dependent BC cells only when these two lines are treated with estrogen but reacts with conditioned medium from several other hormone-independent cell lines in the absence of estrogen stimulation. This MCA is currently undergoing further characterization and evaluation of its biological potency. We conclude that with estrogen stimulation, hormone-dependent human BC cells secrete peptides which when partially purified can replace estrogen as a mitogen. Their role as autocrine or paracrine growth factors and their effects on surrounding nonneoplastic stroma may suggest a means of interfering with tumor proliferation. |
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