Phenotypic heterogeneity in breast fibroblasts: Functional anomaly in fibroblasts from histologically normal tissue adjacent to carcinoma
Version of Record online: 17 JUL 2006
Copyright © 1994 Wiley-Liss, Inc., A Wiley Company
International Journal of Cancer
Volume 59, Issue 1, pages 25–32, 1 October 1994
How to Cite
Schor, A. M., Rushton, G., Ferguson, J. E., Howell, A., Redford, J. and Schor, S. L. (1994), Phenotypic heterogeneity in breast fibroblasts: Functional anomaly in fibroblasts from histologically normal tissue adjacent to carcinoma. Int. J. Cancer, 59: 25–32. doi: 10.1002/ijc.2910590107
- Issue online: 17 JUL 2006
- Version of Record online: 17 JUL 2006
- Manuscript Revised: 18 MAY 1994
- Manuscript Received: 28 MAR 1994
- Cancer Research Campaign and the Christie Hospital Endowment Fund.
Histologically normal breast tissue was obtained from women undergoing surgery for benign breast lesions (n = 12) and mammary carcinomas (n = 15). Four fibroblast subpopulations (FI, FII, FIII and FIV) were isolated from these specimens by differential digestion and centrifugation. FI cells were the first to be released from the tissue digest and consequently assumed to be derived from the interlobular stroma; FIV fibroblasts were tightly associated with the epithelial organoids and are therefore believed to be of intralobular origin. These cells were characterised in terms of their migratory phenotype (classified as either foetal- or adult-like) and the production of motility factors according to previously described techniques. FI fibroblasts obtained from patients with benign breast lesions displayed a foetal migratory phenotype (10/11) and secreted detectable quantities of motility factors (11/11). In contrast, none of the FIV fibroblasts (0/10) obtained from these same patients displayed a foetal-like migratory phenotype or secreted motility factors. In the case of fibroblasts obtained from cancer patients, both FI (13/13) and FIV (13/13) fibroblasts displayed a foetal-like migratory phenotype and secreted motility factors. Fibroblasts were also derived from skin (n = 12) and breast fat tissue (n = 4) of certain patients. In agreement with our previously published observations, skin fibroblasts obtained from non-cancer and cancer patients also differed in terms of their migratory behaviour: none of the skin fibroblast lines (0/5) obtained from non-cancer patients were foetal-like, compared to 3/7 lines from cancer patients. All fat-derived fibroblasts (I non-cancer and 3 cancer patients) were also foetal-like. Our results indicate (i) functional heterogeneity between FI and FIV fibroblasts of normal breast, and (ii) the presence of functionally aberrant (i.e., foetal-like) FIV fibroblasts in histologically normal breast tissue adjacent to a carcinoma.