EXPRESSION OF AND RESPONSE TO INTERLEUKIN-6 (IL6) IN HUMAN MAMMARY-TUMORS

Multifunctional cytokines play important and only partially defined ro les in mammary tumor development and progression. Normal human mammary epithelial cells (MECs) constitutively produce interleukin (IL) 6, IL 8, and a nonsecreted form of tumor necrosis factor. MEC transformation by different oncogenes is frequently associated with alterations of c ytokine growth factor production and responsiveness. This seems partic ularly true in the case of IL6. Histochemical studies showed that expr ession of immunoreactive IL6, as compared to normal tissue and to in s itu lesions, is significantly reduced in invasive ductal carcinoma. Co nversely, the expression of IL6 in invasive lobular carcinoma was enha nced. Expression of TGP-beta 1 in mammary neoplasia was In general les s intense than that seen in the normal mammary gland. In vitro studies partially supported the in vivo findings: expression of IL6 and TGF-b eta 1 was significantly down-regulated in cultures derived from both d uctal carcinoma and peritumoral tissue. Similarly, responsiveness to I L6 and TGF-beta 1 was significantly reduced in neoplastic MECs. The da ta suggest that alterations of cytokine pathways are present not only in mammary neoplasia, but also in pathologically unaffected breast tis sues.