Effects of Chemotherapy on Tumor Stromal Cells in Breast Cancer Patients

Background: Tumor stromal cells (TSCs) are a heterogenous population of non-cancer cells that exist within the tumor microenvironment. TSCs have a role in cancer development, progression and survival by a variety of mechanisms. Their expression of the cell surface markers GP38, PDGFR- #945;, PDL-1 and CD29 have been implicated in these processes. This study aims to establish what effect the chemotherapeutics; doxorubicin, paclitaxel and 5-FU have on the expression levels of these markers. Methods: Core biopsies from the tumor mass (TSC) and distant breast tissue (TAN) were obtained from 2 patients undergoing curative surgery for breast cancer. Stromal cells were isolated and incubated. Once cell growth was established, a fixed number (5x105) of both cell populations were exposed to 1µM or 5µM paclitaxel, 1 µM or 5 µM 5-FU and 1 µM or 10 µM doxorubicin for 24hours. After this period cells were harvested and expression of the cell surface markers of interest was carried out by flow cytometry. Results: In untreated TSCs and TANs the mean Mean Flourescence Intensitys for PDL-1, GP38, CD29 and PDGFRa were (TSCvTAN) (1476v1019), (7322v11421), (158954v148313), (749v2552) respectively. Exposure to 1µM and 5 µM Paclitaxel produced MFIs of were TSCvTAN (236v143), (606v425), (15919v15914) and (45.6v49.1) respectively at 1 µM and (252v147), (602v379), (16185v16410) and (43.5v43.1) at 5 µM). Exposure to 1µM and 5 µM 5FU produced and mean MFIs of (3421v1315), (15924v16983), (191245v179943) and (2394v933) at 1 µM. At 5 µM the mean MFIs were (1237v1425), (14719v18033), (125808v265000) and (21569v641) respectively. Finally, Exposure to 1µM and 10 µM Doxorubicin produced a mean MFIs of (3589v1530), (16312v17752), (212258v204133) and (1911v644) at 1 µM and (1381v1640), (14434v18682), (82055v81492) and (2173v113) for 10 µM Doxorubicin. Conclusion: Any contribution made to the tumorigenesis by TSC overexpressing PDL-1 and GP38 is unimpaired by exposure to adjuvant chemotherapy in breast cancer. No change is seen when you introduce chemotherapy to the cell surface receptors.