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Co‐culture with human fibroblasts increases the radiosensitivity of MCF‐7 mammary carcinoma cells in collagen gels
Author(s) -
Rossi Lorenzo,
Reverberi Daniele,
Podestá Giorgia,
Lastraioli Sonia,
Corvó Renzo
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000301)85:5<667::aid-ijc12>3.0.co;2-1
Subject(s) - radiosensitivity , stromal cell , cell culture , fibroblast , cancer associated fibroblasts , mcf 7 , carcinoma , biology , tissue culture , microbiology and biotechnology , cell growth , pathology , cancer research , chemistry , cancer cell , in vitro , medicine , human breast , radiation therapy , cancer , tumor cells , biochemistry , tumor microenvironment , genetics
The growth and differentiation of normal and neoplastic epithelial cells may be regulated by the presence of adjacent normal tissues and cells, particularly stromal fibroblasts. However, the influence of normal fibroblast–tumor cell interactions on the response of malignant epithelial cells to radiation has not been adequately investigated nor has the possible role played by a 3‐D environment in such modulation. We addressed this question by embedding MCF‐7 mammary carcinoma cells into a collagen lattice, alone or mixed with HSF human dermal fibroblasts, and kept the gels anchored to the plastic surface or suspended in the culture medium. Some gels served as controls and others were irradiated with 6 MV photons fractionated into 3 daily doses totaling 5 or 10 Gy. After 2 or 7 days from the last treatment (7 or 12 days in culture, respectively), gels were processed in 1 of 2 ways: overall cell survival was determined by the MTT assay, while the survival of MCF‐7 cells was selectively detected by a clonogenicity assay. Under these experimental conditions, we found that, in the presence of HSF fibroblasts, the growth of MCF‐7 cells was restrained and radiosensitivity increased compared with MCF‐7 cells cultured alone. For example, while the average number of MCF‐7 foci/gel recovered from control gels with MCF‐7 cells alone was 2,460 on day 7 and 3,290 on day 12 of culture, it was 4 to 5 times lower ( p < 0.001) in control gels with mixed MCF‐7 and HSF cells. Radiation affected severely the survival of MCF‐7 cells in all experimental groups but not sufficiently to mask the differences. For example, following exposure to the low dose of 5 Gy, the average number of MCF‐7 foci/gel recovered from MCF‐7‐containing gels was 590 on day 7 and 329 on day 12 of culture, whereas numbers from the gels containing mixed MCF‐7 and HSF cells were only 218 and 73, respectively ( p < 0.003 in both cases). HSF fibroblasts did not grow in our system, but they contracted strongly anchored and floating gels. Int. J. Cancer 85:667–673, 2000. © 2000 Wiley‐Liss, Inc.