CMTM6 is a membrane protein that acts as a regulator of PD-L1, maintaining its expression on the cell surface, and can prevent its lysosome-mediated degradation. It is unknown if CMTM6 is present in the plasma of patients with cervical cancer, and if it has non-canonical subcellular localizations in cell lines derived from cervical cancer. Our objective was to determine whether CMTM6 is found in plasma derived from cervical cancer patients and its subcellular localization in cell lines. Patient plasma was separated into exosome-enriched, exosome-free, and total plasma fractions. The levels of CMTM6 in each fraction were determined using ELISA and Western blot. Finally, for the cellular model, HeLa, SiHa, CaSki, and HaCaT were used; the subcellular locations of CMTM6 were determined using immunofluorescence and flow cytometry. Soluble CMTM6 was found to be elevated in plasma from patients with cervical cancer, with a nearly three-fold increase in patients (966.27 pg/mL in patients vs. 363.54 pg/mL in controls). CMTM6 was preferentially, but not exclusively, found in the exosome-enriched plasma fraction, and was positively correlated with exosomal PD-L1; CMTM6 was identified in the membrane, intracellular compartments, and culture supernatant of the cell lines. These results highlight that CMTM6, in its various presentations, may play an important role in the biology of tumor cells and in immune system evasion.
CMTM6是一种膜蛋白，作为PD-L1的调控因子，能维持其在细胞表面的表达，并防止其发生溶酶体介导的降解。目前尚不清楚CMTM6是否存在于宫颈癌患者的血浆中，以及在宫颈癌细胞系中是否存在非经典亚细胞定位。本研究旨在检测宫颈癌患者血浆中CMTM6的存在情况及其在细胞系中的亚细胞定位。将患者血浆分离为外泌体富集组分、无外泌体组分及全血浆组分，采用ELISA和Western blot检测各组分中CMTM6水平。细胞模型选用HeLa、SiHa、CaSki和HaCaT细胞系，通过免疫荧光和流式细胞术确定CMTM6的亚细胞定位。结果显示，宫颈癌患者血浆中可溶性CMTM6水平显著升高（患者组966.27 pg/mL vs 对照组363.54 pg/mL，升高近三倍）。CMTM6主要富集于外泌体组分（但不仅限于此），且与外泌体PD-L1呈正相关；在细胞系的膜结构、胞内区室及培养上清中均检测到CMTM6。这些结果表明，CMTM6可能通过多种存在形式在肿瘤细胞生物学行为及免疫逃逸中发挥重要作用。
肿瘤(癌症)患者之家