Pilot Study on Factors Secreted by Differentiating Mammary Epithelial Cells (MECs) That Can Suppress Proliferation of Breast Cancer Cells

In normal cells, proliferation and differentiation are regulated and coordinated in a way that activation of differentiation in normal cells is typically associated with cessation of proliferation. However, the balance between the two is usually disrupted in tumorigenesis, ultimately leading to a complex cellular phenotype typical of cancer cells. In attempts to identify the differentiation-inducing factors in conditioned medium, conditioned medium was fractioned and applied to breast cancer cell, MCF7, cultured in Matrigel. Unexpectedly, a cytotoxic activity was observed on MCF7 cells treated with the fraction of molecular weight between 10- 50kDa after seven days. In the past year, I first confirmed the cytotoxicity on various breast cancer cell lines with different genetic backgrounds, including MD-AMB-468 and SKBR3. From mass spectrometric analysis on this 10-50kDa fraction of the conditioned medium, six factors such as interleukins (ILs), bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs) and other cytokines, which are known to be involved in cell proliferation and death, have been selected as proteins of interests and their cytotoxic activities were confirmed by immunodepletion. Chinese hamster ovary (CHO) cells overexpressing each of the six factors have been established for future reconstitution experiments and animal studies.