Smooth‐muscle differentiation in stromal cells of malignant and non‐malignant breast tissues

Abstract

A mouse monoclonal antibody (MAb) recognizing alpha-smooth-muscle actin has been used to study smooth-muscle differentiation features in the stromal cells of desmoplastic reactions accompanying mammary tumors. We have studied, by the same immunohistochemical technique, a series of malignant and non-malignant human breast tissues. Cells composing the desmoplastic reaction were found to express alpha-smooth-muscle actin in all the 11 breast carcinomas examined, whereas no immunostain was demonstrated in the stromal cells of 7 breast tissue samples histologically defined as normal. Three of 9 cases of fibrocystic disease showed a minority of positively stained stromal cells, generally in association with epithelial hyperplasia. All the 7 cases of sclerosing adenosis, 3 of 4 cases of diffuse papillomatosis and all 3 intraductal papillomas exhibited a majority of immunoreactive stromal cells. Numerous stromal cells in 3 of 11 circumscribed fibroadenomas analyzed expressed low amounts of alpha-smooth-muscle actin. The factor(s) responsible for smooth-muscle differentiation in stromal cells are presently unknown, but the detection of this previously unsuspected stromal cell phenotype in nonmalignant mammary tissues might help in characterizing the variant morphological aspects designated under the label "fibrocystic disease" and in understanding the biology of premalignant or early malignant lesions of the breast.

Tumor-Secreted LOXL2 Activates Fibroblasts through FAK Signaling

“…CAFs are themselves a heterogeneous population of cells with a varying number being referred to as activated fibroblasts or myofibroblasts due to expression of a-smooth muscle actin (a-SMA; refs. [6][7][8].…”

Activation of Notch1 signaling in stromal fibroblasts inhibits melanoma growth by upregulating WISP-1

“…Quiescent Fbs are activated and recruited the MSCs are induced to differentiate into Fbs. Activated Fbs (also known as CAF) actively produce growth factors, cytokines/ chemokines, extracellular matrix and express a-smooth muscle actin and vimentin (Sappino et al, 1988). The biological behaviors of Fbs can be regulated by a variety of signals.…”

A Hybrid Model of Tumor–Stromal Interactions in Breast Cancer

“…These "tumor-associated-fibroblasts" (TAFs) play a role in a perceived "greater infiltrative potential" for comedo DCIS when compared to noncomedo DCIS, both by secretion of paracrine factors detected by tumor cells, and by alterations to the ECM. Myofibroblasts, which are characterized as activated fibroblasts with the phenotypic characteristics of smooth muscle differentiation, are abundant in the stroma of malignant breast tissue, but rarely seen in normal breast tissue (Sappino et al 1988). Active proliferation of myofibroblasts and in turn, increased collagen deposition near tumor regions, are characteristics of many solid tumors (Tlsty 2001).…”