Background: Tumor-associated macrophages (TAMs) are major inflammatory cells in tumor microenvironment (TME). PLCL (phospholipase C-like protein) suppresses the PI3K-AKT-mTORC1 signaling, which negatively regulates tumor cell proliferation and survival. In this study, we investigated the relationship between the expression of PLCL in human tumor tissues or TAM and tumor metastasis.
Methods: Renal cell carcinoma (RCC) tissues (30 cases, Approval of Kyusyu Univ. Hospital) were used. PLCL-positive areas were automatically calculated by a hybrid cell count. PLCL-positive TAMs in TME were performed by fluorescent multiplex immunostaining. TAM induction was analyzed when bone marrow derived macrophages (BMDMs) of PLCL-KO or WT mice were co-cultured with Caki1 (renal cancer cells without metastasis) or OSRC2 (renal cancer cells with metastasis).
Results: PLCL expression in tumor area was markedly decreased in the cases with metastasis compared to non-tumor area. This was not seen in non-metastatic cases. PLCL-positive TAM rate in the TME was different between the cases with and without metastasis. In addition, BMDM from PLCL-KO mice co-cultured with OSRC2 was most induced to TAM.
Conclusion: We indicated that decreased expression of PLCL in RCC mediates tumor malignancy, and less PLCL expression in TAMs exacerbates TME leading to tumor progression and malignant transformation. Hence, a drug enhancing PLCL expression can be effective new cancer therapeutics for RCC.