Abnormal properties of skin fibroblasts from patients with breast cancer

Abstract

The growth properties of fibroblasts from the thoracic skin of patients with mammary cancers were compared to those of fibroblastic cultures from patients with benign lesions or having undergone surgery for non-neoplastic diseases. As expected, an inverse correlation was found between the doubling potential of fibroblasts in vitro and the donor's age for cells from patients with benign lesions; however no correlation, was found with cultures from cancer patients. Moreover, the latter group responded in an abnormal way to three biological parameters: anchorage dependence, colony formation on monolayers of normal human epithelial cells and saturation densities in overcrowded culture conditions. Skin fibroblasts from one patient with a benign lesion, whose mother had developed a breast cancer, displayed all the abnormal growth properties. Periodic controls of this patient resulted in the early detection of a carcinoma 3 years after the first operation for a benign microcystic lesion. Finally, we found that multiple subcultivations in overcrowded culture conditions cause the selection of a fibroblastic cell subset with greater growth potential which, in the cell strain tested, could invade foreign tissue in vitro.

Role of cancer-associated fibroblasts in breast cancer development and prognosis

“…It is well known that there is a genetic component in the predisposition to breast cancer. Indeed, skin fibroblasts derived from breast cancer patients may also be altered and exhibit characteristics associated with a transformed phenotype (Azzarone et al, 1984). In another study, skin fibroblast cells derived from breast cancer patients exhibited higher sensitivity to irradiation than skin fibroblastic cells from healthy women (Hannan et al, 2001).…”

Macro-environment of breast carcinoma: frequent genetic alterations in the normal appearing skins of patients with breast cancer

“…Indeed, abnormal skin fibroblasts displaying various oncofetal characteristics were demonstrated in 90% of patients with familial breast cancer and 50% of the clinically unaffected firstdegree relatives of patients suffering from familial breast cancer. [6][7][8][9] Moreover, abnormal skin fibroblasts with a high level of enhanced reactivation of herpes simplex virus have been found in a variety of hereditary cancer-prone syndromes such as retinoblastoma, polyposis coli, neurofibromatosis type 1 and 2, dysplastic nevus syndrome, von HippleLindau syndrome, and multiple endocrine neoplasia type 2, suggesting that loss of one allele of putative TSGs may activate cellular processes that result in the induction of the enhanced reactivation response and that functionally abnormal skin fibroblasts may be related to the process of carcinogenesis. 28 The frequent genetic alterations in the skin, particularly LOH near some of the putative TSGs, as identified in our study, may partly explain some of the abnormal fibroblastic functions that have been observed in the skin of patients with breast cancer or some of the cancer-associated hereditary diseases.…”

“…[6][7][8][9] Indeed, abnormal properties of skin fibroblasts displaying various oncofetal characteristics such as invasion of embryonic organ culture and increase of saturation densities in overcrowded culture conditions were demonstrated in 90% of patients with familial breast cancer and in 50% of the clinically unaffected firstdegree relatives of patients suffering from familial breast cancer. [6][7][8] The genetic basis of this phenomenon, however, has not yet been explored. In this report, we present the first data concerning the frequent occurrence of LOH and microsatellite instability (MSI) in the normal skin (epidermis/dermis) of breast cancer patients.…”

Saturation Density of Skin Fibroblasts as a Quantitative Screen for Human Cancer Susceptibility

“…Living cells, however, integrate the phenotypic effects of many genes, and long-standing evidence is presented that increased saturation density (SD, the maximum number of cells in a culture, limited by contact inhibition and the concentration of serum in the medium) of skin fibroblasts (SF) is displayed both in the case of the high penetrance of a single mutated gene in cancerprone families (7,8), and of multiple mutated genes in "sporadic" breast (9) and other cancers (10). Increases in SD result from selection of cells under contact inhibition of mutants that mainly arise during the replication of cells (11,12).…”