Association between growth factor heregulin1α and receptors in growth of ovarian cancer cell line with high potentiality of peritoneal dissemination.

Ovarian cancer, one of the poor-prognosis gynecological malignancies, is often associated with extensive peritoneal carcinomatosis when initially treated. The mechanism of the formation of peritoneal carcinomatosis from ovarian cancer is still unknown. It has been reported that overexpression of cancer-related growth factors and/or receptors may worsen the prognosis of diseases. In the previous paper, we had established the human ovarian serous adenocarcinoma cell lines from those with no potentiality of peritoneal dissemination (FOC-3) to high potentiality (MFOC-3), however, the mechanism of its phenotypical change remains unknown. In this paper, we compared these two cell lines for growth potential and the expression of growth factor heregulin (HRG)-1α and HER-2, HER-3, and HER-4 receptors. In addition, the effect of anti-receptor antibodies on cell growth was investigated. RT-PCR and Western blot analysis found the promotion of the expression of HRG precursor and HRG-1α in MFOC-3. Examination of the number of growing cells over time revealed a statistically significant increase in the number of cells in MFOC-3 compared with FOC-3. In a study using the addition of exogenous HRG-1α, no changes were observed in FOC-3 while statistically significant cell growth was noted in MFOC-3. In a growth inhibition study, statistically significant cell growth inhibition was achieved with the addition of anti-HER2 receptor antibody. Taken together, the results of this study suggested that HRG may play an important role in the increased growth potential of peritoneal dissemination of ovarian cancer. In particular, HER-2 receptors that can act as a starting point to trigger intracellular signaling pathways are strongly involved in the progression of cancer. Therefore, molecular target drug therapies blocking the HER-2 receptor are promising candidates for ovarian cancer treatment in the future.