PHENOTYPIC HETEROGENEITY IN BREAST FIBROBLASTS - FUNCTIONAL ANOMALY IN FIBROBLASTS FROM HISTOLOGICALLY NORMAL TISSUE ADJACENT TO CARCINOMA

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 iso lated from these specimens by differential digestion and centrifugatio n. FI cells were the first to be released from the tissue digest and c onsequently assumed to be derived from the interlobular stroma; FIV fi broblasts were tightly associated with the epithelial organoids and ar e therefore believed to be of intralobular origin. These cells were ch aracterised in terms of their migratory phenotype (classified as eithe r foetal- or adult-like) and the production of motility factors accord ing to previously described techniques. FI fibroblasts obtained from p atients with benign breast lesions displayed a foetal migratory phenot ype (10/11) and secreted detectable quantities of motility factors (11 /11). In contrast, none of the FIV fibroblasts (0/10) obtained from th ese same patients displayed a foetal-like migratory phenotype or secre ted motility factors. In the case of fibroblasts obtained from cancer patients, both FI (13/13) and FIV (13/13) fibroblasts displayed a foet al-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 observat ions, skin fibroblasts obtained from non-cancer and cancer patients al so differed in terms of their migratory behaviour: none of the skin fi broblast lines (0/5) obtained from non-cancer patients were foetal-lik e, compared to 3/7 lines from cancer patients. All fat-derived fibrobl asts (1 non-cancer and 3 cancer patients) were also foetal-like. Our r esults indicate (i) functional heterogeneity between FI and FIV fibrob lasts of normal breast, and (ii) the presence of functionally aberrant (i.e., foetal-like) FIV fibroblasts in histologically normal breast t issue adjacent to a carcinoma. (C) 1994 Wiley-Liss, Inc.