Role of Mast Cells in Shaping the Tumor Microenvironment
Role of Mast Cells in Shaping the Tumor Microenvironment
复制标题
DOI：
10.1007/s12016-019-08753-w
复制
发表时间：
2020-06-01
影响因子：
9.1
通讯作者：
Redegeld, Frank A.
中科院分区：
文献类型：
--
作者：
Komi, Daniel Elieh Ali;Redegeld, Frank A.
早期肥大细胞（MC）浸润已被报道在广泛的人类和动物肿瘤，特别是恶性黑色素瘤和乳腺癌和结直肠癌。它们存在于肿瘤微环境（TME）或其边缘的后果仍然不清楚，因为它与基于肿瘤类型和解剖部位的良好或不良预后相关。在肿瘤内，MC与浸润的免疫细胞、肿瘤细胞和细胞外基质（ECM）通过直接细胞间相互作用或释放能够重塑TME的广泛介质而发生相互作用。MC通过释放经典的促血管生成因子（包括VEGF、FGF-2、PDGF和IL-6）和非经典的促血管生成因子（主要是蛋白酶，包括类胰蛋白酶和糜蛋白酶）来积极促进血管生成并诱导新血管形成。MC通过释放广泛的基质金属蛋白酶（MMPs）支持肿瘤侵袭。当假设通过酪氨酸激酶抑制剂（伊马替尼和马赛替尼）和类胰蛋白酶抑制剂（加贝酯和甲磺酸萘莫司他）控制其活化或控制其与其他细胞类型的相互作用可能具有治疗益处时，肿瘤内MC的存在获得了额外的意义。
Early mast cell (MC) infiltration has been reported in a wide range of human and animal tumors particularly malignant melanoma and breast and colorectal cancer. The consequences of their presence in the tumor microenvironment (TME) or at their margins still remain unclear as it is associated with a good or poor prognosis based on the type and anatomical site of the tumor. Within the tumor, MC interactions occur with infiltrated immune cells, tumor cells, and extracellular matrix (ECM) through direct cell-to-cell interactions or release of a broad range of mediators capable of remodeling the TME. MCs actively contribute to angiogenesis and induce neovascularization by releasing the classical proangiogenic factors including VEGF, FGF-2, PDGF, and IL-6, and nonclassical proangiogenic factors mainly proteases including tryptase and chymase. MCs support tumor invasiveness by releasing a broad range of matrix metalloproteinases (MMPs). MC presence within the tumor gained additional significance when it was assumed that controlling its activation by tyrosine kinase inhibitors (imatinib and masitinib) and tryptase inhibitors (gabexate and nafamostat mesylate) or controlling their interactions with other cell types may have therapeutic benefit.