Differential tissular expression and localization of type IV collagen alpha(IV), alpha 2(IV), alpha 5(IV), and alpha 6(IV) chains and their mRNA in normal breast and in benign and malignant breast tumors

Type IV collagen, the major component of basement membrane (BM), is compose d of six genetically distinct a chains. We investigated the cellular regula tion and origin of these alpha(IV) chains in normal and neoplastic breast t issues by immunohistochemistry by using alpha(IV) chain-specific antibodies and by in situ hybridization. In normal breast, alpha 1(IV) and alpha 2(IV ) chains were stained in all BM, whereas alpha 5(IV) and alpha 6G(IV) chain s were restrictively localized in a linear pattern in the BM of the mammary gland. Similar immunostaining profiles were observed in benign breast tumo rs and in the intraductal components of invasive ductal carcinoma. However, in invasive ductal carcinoma, alpha 1(IV) and alpha 2(IV) chains were disc ontinuously or negatively stained in the cancer cell nests, and the assembl y of alpha 5(IV) and alpha 6(IV) chains into the BM was completely inhibite d. Coexpression of alpha 5(IV) and alpha 6(IV) chains was related to the lo calization of alpha-smooth muscle actin (alpha-SMA)-positive myoepithelial cells. By in situ hybridization, in fibroadenoma and invasive ductal carcin oma, the signals for alpha 1(IV) and alpha 2(IV) mRNA were abundant in stro mal cells. However, the signals for alpha 5(IV) and alpha 6(IV) mRNA were n ot seen in any of these cells. In contrast, in intraductal papilloma, coexp ression of alpha 1(IV)/alpha 2(IV) mRNA and alpha 5(IV)/alpha 6(IV) mRNA wa s identified in epithelial cells. The results indicate that the mammary gla nd forms a second network of BM composed of alpha 5(IV)/alpha 6(IV) chains, in addition to the classic network of alpha 1(IV)/alpha 2(IV) chains. The expression of type IV collagen alpha chains seems to be differentially regu lated by the epithelialmyoepithelial interaction and to be associated with the invasive potential of breast cancer.