肿瘤转移前龛环境的正虚痰瘀病机探讨

Discussion on pathogenesis of deficiency of healthy-qi and stagnation of phlegm&blood in tumor pre-metastatic niche

“正气存内,邪不可干”。肿瘤转移前龛环境以正虚为本,痰瘀为标,是易化与协助肿瘤传舍的关键病机。肿瘤分泌因子、外泌体动员髓源抑制细胞(MDSCs)和调节性T细胞(Tregs)在龛环境聚集,抑制效应T细胞与自然杀伤细胞(NK)的活化及细胞毒作用,形成以免疫抑制为特征的正气不足“龛虚”微环境;发生上皮间质转化的肿瘤循环细胞(CTCs)为流注之“虚邪”,“两虚相得乃客其形”,肇始肿瘤传舍。肿瘤细胞释放的组织因子激活凝血酶系统,活化血小板,与CTCs及纤维蛋白形成CTCc聚集体在血管瘀积、黏附,增加血管通透性,营造凝涩、黏着、渗漏的“血瘀”微环境。致瘤性炎症募集免疫抑制细胞,慢性炎性“闷烧”内生无形之痰,流动不测;细胞外基质重构致龛环境纤维化,痰浊结聚,黏滞难去,痰挟瘀血,遂为窠囊。肿瘤胞外微泡是肿瘤转移信使,预谋龛虚痰瘀,蓄意传舍癌毒,暗指转移方位。上工治未病,“务先安未受邪之地”,扶正是改善龛虚微环境之本,化痰活血并依转移靶器官之不同加入引经之药,方可“救其萌芽”。

The internal healthy-qi eliminates pathogens.The deficiency of healthy-qi and stagnation of phlegm and blood are the pathogenesis of tumor pre-metastatic niche.The accumulation of myeloid-derived suppressor cells(MDSCs)and regulatory T cells(Tregs)facilitates the formation of‘niche-deficiency’microenvironment by blocking the stimulation of effector T cells and impairing their cytotoxic effects.The pre-metastatic niche together with circulation tumor cells(CTCs)that carrying epithelial-to-mesenchymal transition(EMT)signals synergistically promote metastasis.The platelets may form aggregates with CTCs and provide protective‘cloak’by neutralizing natural killer cell(NK)-mediated killing.Platelet and inflammatory cellderived growth factors and cytokines increase the tumor cell adhesion and extravasation via upregulating adhesion molecules and increasing endothelial permeability.Tumor-promoting inflammation recruits immunosuppressive cells to smother the flame and leads to a‘phlegm-congealing’microenvironment with high viscosity and capriciousness.Tumor-derived extracellular vesicles are vanguards to promote the crosstalk between the primary tumor and the metastatic niche.The tumor exosome integrins may determine metastatic organotropism and carry oncogenic cargoes.Adhere to‘stabilizing the uninfected area takes precedence’,invagorating healthy-qi is of choice to ameliorate pre-metastatic niche.Promoting blood circulation and resolving phlegm together with guiding herb are preferred to suppress metastasis in its infancy.