Human chorionic gonadotropin induces melanoma growth

QADRANA, FLORENCIA M; NICOLA CANDIA, ALEJANDRO J; JURIOL, LORENA; HEGER, JULIA; VENTIMIGLIA, MARÍA SILVIA; CANDOLFI, MARIANELA; JENSEN, FEDERICO

Congreso; Reunión anual de la SAIC; 2018

Melanoma is the leading cause of neoplasia in women within reproductive age and the most frequently diagnosed malignancy during pregnancy. However, the physiological mechanism behind this phenomenon remains unknown.We aimed to investigate here the role of pregnancy-associated hormone, human chorionic gonadotropin (hCG), in melanoma behavior.Mouse metastatic melanoma cell line (B16-F10) was cultured with hCG (10 IU) or PBS for 24, 48 and 72 h. Proliferation rate was evaluated by flow cytometry (FC) using CFSE staining. Besides, expression levels of PD-L1 and PD-1 on B16-F10 cells were also measured by FC. Each experiment was performed in duplicates and repeated three times. Additionally, virgin 8-10 weeks old C57BL/6 females were subcutaneously injected with 2X105 B16-F10 cells and challenged (IP) every second day with hCG (10 IU) or PBS (n=6 each group). Tumor volume was daily monitored and animals were sacrificed 22 days after tumor injection. Tumor and spleen tissues were dissected weighted and mechanically disaggregated using 70-μm nylon filters. Obtained cells were stained with specific antibodies against CD45, CD3, CD19, CD4, CD8, Foxp3, NK.1.1, CD11c, PD-1, PD-L1 and analyzed by FC. Mann. Whitney or t-tests were applied to compare groups.We observed that hCG treatment neither affects proliferation rate nor provoked changes on PD-1/PD-L1 expression in B16-F10 cells in vitro. However, tumor-bearing female mice treated with hCG depicted a significantly higher tumor volume and tumor weight as compared to PBS-treated control mice. Furthermore, hCG-treated mice showed significantly lower numbers of tumor infiltrating leukocytes (TIL) as compared to control animals. Systemically, hCG-treated mice showed significantly lower percentages of CD19+ B and CD3+ T lymphocytes in the spleen. Additionally, splenic CD3+CD8+ T cells expressed higher levels of PD-1 compared to controls.Our results clearly demonstrate that pregnancy-associated hormone (hCG) induces melanoma growth by a mechanisms