Galectin-3介导的多核型髓源抑制细胞在宫颈癌淋巴结转移前微环境中的作用及其机制研究

Lymph node metastasis contributes largely to the mortality of cervical cancer patients. Researchers have discovered that polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs) could promote tumor metastasis via forming pre-metastatic niche. However, the effect of PMN-MDSCs on forming pre-metastatic niche in cervical cancer lymph nodes has not been revealed. Our pre-experiments demonstrated that tumor-secreted factor Galectin-3 was significantly upregulated in pre-metastatic niche in cervical cancer lymph nodes and could recruit PMN-MDSCs. Our previous study also showed that Galectin-3 was corelated to lymph node metastasis in cervical cancer patients and dramatically promoted cervical cancer metastasis. Therefore, we assume that Galectin-3 may form pre-metastatic niche in cervical cancer lymph nodes through recruiting PMN-MDSCs, promoting cervical cancer lymph node metastasis. On the basis of this hypothesis, the present project intends to further clarify the mechanism of Galectin-3 recruiting PMN-MDSCs through activating integrin αVβ3/c-Src/STAT3 pathway, promoting lymphogenesis and forming immune suppressive pre-metastatic niche in cervical cancer lymph nodes. This project would discover novel mechanism of oriented lymph node metastasis in cervical cancer from the perspective of pre-metastatic niche, providing potential diagnosis and treatment target for cervical cancer patients with lymph node metastasis.

淋巴结转移是宫颈癌患者致死的主要原因。研究发现多核型髓源抑制细胞（PMN-MDSCs）可构筑转移前微环境而促进肿瘤转移。然而，PMN-MDSCs在宫颈癌淋巴结转移前微环境中的作用尚未阐明。我们预实验发现，肿瘤分泌因子Galectin-3在宫颈癌淋巴结转移前微环境中高度表达并能够募集PMN-MDSCs。前期研究也证明，Galectin-3与宫颈癌淋巴结转移高度相关并可明显促进宫颈癌转移。由此，我们推测：Galectin-3可能通过募集PMN-MDSCs促宫颈癌淋巴结转移前微环境形成，进而定向转移。因此，本项目拟进一步阐明Galectin-3通过integrin αVβ3/c-Src/STAT3招募PMN-MDSCs促进淋巴血管新生及构筑免疫抑制的宫颈癌淋巴结转移前微环境的机制。本研究从转移前微环境角度揭示宫颈癌淋巴结定向转移的新机制，为宫颈癌患者提供潜在的淋巴结转移预警分子及精准治疗靶点。

淋巴结转移是宫颈癌患者致死的主要原因。研究发现多核型髓源抑制细（PMN-MDSCs） 可构筑转移前微环境而促进肿瘤转移。然而，PMN-MDSCs在宫颈癌淋巴结转移前微环境中的作用尚未阐明。.本项目阐明了肿瘤来源分泌分子Galectin-3 可经循环系统进入淋巴结内，通过 integrin αVβ3/c-Src/STAT3通路招募 PMN-MDSCs 并使其持续增殖，促进局部淋巴血管新生及构筑免疫抑制的转移前微环境，进而招募更多的宫颈癌细胞发生淋巴结定向转移。本研究从转移前微环境角度揭示宫颈癌淋巴结定向转移的新机制，为宫颈癌患者提供潜在的淋巴结转移预警分子及精准治疗靶点。