Role of the Mammary Adenocarcinoma Cell Transferrin Response in Breast Cancer Metastasis.

摘要

We had previously found that breast cancer cell expression of the transferrin receptor (TfR) and/or ability to proliferate in response to transferrin (Tf) correlated with the metastatic capabilities of the cells. We desired to elevate or lower breast cancer cell TfR expression using various techniques, and to assess as to whether or not these changes affected metastatic capability. The human MDA231 mammary adenocarcinoma cell line was transfected with a plasmid carrying the cDNA for human TfR in the sense orientation. High TfR expressors (MDA231/TfR) were selected by FACS, and were shown to express 6- 12 times more TfR than did vector transfected control cells (MDA231/Neo). MDA231/TfR cells were observed to be able to proliferate in serum-free media via a non-Tf dependent mechanism whereas MDA231/Neo could not. When injected into the mammary fat pad of nude mice, both lines produced 10 tumors, however, MDA231/TfR cells formed frequent intra-peritoneal and lung micrometastases whereas MDA231/Neo cells formed only occasional lung micrometastases. Increasing cell surface TfR on the MDA231 cell line promoted cell serum-free growth and metastatic ability.