Abstract 1320
Background
The ovarian microenvironment is influential on ovarian cancer progression and metastases as it offers a rich niche of pro inflammatory markers potentiating angiogenesis, growth and tumour progression. We sought to investigate the malleable nature of stromal cells analyzing the paracrine communication with granulosa cells and its autocrine regulation in stromal cells using conditioned medium studies.
Methods
Primary stromal cells were cultured from wild type mice C57BL/6J. Cultured stromal cells were treated with conditioned media from stromal cells (CMSC), conditioned media of preantral granulosa cells (CMPAGC), conditioned media of pre ovulatory granulosa cells (CMPOGC) and conditioned media of ovarian explants (CMOE). The treatment effects on cell proliferation were analyzed with WST 1 assay. Western blot on stromal cell lysates was performed for analyzing its treatment responses to conditioned media CMSC, CMPAGC, CMPOGC, CMOE assessing pERK, pAKT, NFKB, GP130 activity.
Results
The control group exhibits a gradual increase in cell proliferation in stromal cells over a 96 hour time course. The CMPOGC & CMPAGC enhances cell growth in stromal cells. In the absence of granulosa cells, CMSC substantially inhibits the growth of the stromal cell population. Western blot analysis of stromal cells treated with CMSC showed a down regulation of GP130 receptor, a reduction in pAKT, pERK and NFKB signaling, in comparison to treatment control groups.
Conclusions
Stromal cells produce a non-inflammatory mediator that suppresses cell growth in the stromal cell population in an autocrine fashion. The tumour microenvironment is a potential source in promoting tumour progression and metastases. Comparisons are needed with stromal cells cultivated from tumour samples. This highlights the need to identify the mediators in CMSC, in pursuit of a drug analogue discovery of a stromal cell inhibitor. This may be a novel targeted therapy in ovarian cancer treatment.
Clinical trial identification
Legal entity responsible for the study
N/A
Funding
University of Miami, Bridge grant
Disclosure
All authors have declared no conflicts of interest.