LOCALIZATION OF THROMBOSPONDIN AND ITS E-SERINE-VALINE-THREONINE-CYSTEIN-GLYCINE-SPECIFIC RECEPTOR IN HUMAN BREAST-CARCINOMA

BACKGROUND: Thrombospondin (TSP), a cell-matrix adhesion protein, and cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG), a major TS P cell adhesive domain, have recently been shown to play a role in tum or cell metastasis. In this study we immunohistochemically localized T SP and its newly discovered CSVTCG-specific receptor in normal, benign , and neoplastic breast tissues. EXPERIMENTAL DESIGN: Paraffin section s of normal, benign, and neoplastic breast tissue were examined immuno histochemically for the presence of TSP and its CSVTCG-specific recept or using the avidin-biotin complex immunoperoxidase staining procedure . RESULTS: Positive staining using polyclonal antibodies for TSP and i ts tumor cell adhesion receptor, isolated from a human adenocarcinoma of the lung, was observed in all primary breast ductal carcinomas exam ined (N = 11). In contrast, all benign lesions and normal breast tissu e stained negative for TSP and its receptor with the exception of two fibrocystic breast samples with hyperplasia. One of the samples showed strong TSP staining of ductal apocrine cells, whereas the other showe d apical receptor staining of hyperplastic ductal cells. The negativel y staining normal and benign tissues consisted of 1 normal breast, 1 g ynecomastia, 5 fibroadenomas, and 6 fibrocystic samples. Positive stai ning for TSP in ductal carcinoma was only localized in the dense strom al collagen adjacent to tumor, whereas the TSP receptor localized to t he tumor cells. Consistent with these immunohistochemical staining res ults was the observation that protein extracts of breast carcinoma cel ls contained receptor with no detectable TSP as revealed by Western bl otting. Capillary endothelium was focally positive for receptor in reg ions proximal to ductal epithelium in 8 of 11 neoplastic tissues and i n 6 of 14 benign samples. CONCLUSIONS: Our results indicate that incre asing expression of stromal TSP and the CSVTCG-specific TSP receptor i n ductal epithelium correlates with neoplastic transformation. In addi tion, our results indicate that both malignant and benign breast tissu e can stimulate surrounding capillaries to express the TSP receptor, w hereas only carcinoma has the capacity to stimulate surrounding nonend othelial stromal cells, such as myofibroblasts, to secrete a TSP-rich matrix that may contribute to the desmoplastic stromal reaction charac teristic of ductal carcinoma tumor. The TSP-rich matrix may then promo te tumor cell attachment, migration, and angiogenesis, factors importa nt in tumor growth. The receptor-rich capillary endothelium may promot e the cell adhesive interactions important in tumor intravasation. Tak en together the results of this study provide a rational basis for a r ole of TSP in tumor angiogenesis and metastasis.