Mammary tumor growth and metastasis are reduced in c-Kit mutant Sash mice.
Mammary tumor growth and metastasis are reduced in c-Kit mutant Sash mice.
复制标题
c-Kit 突变 Sash 小鼠乳腺肿瘤生长和转移减少
作者：
He L;Zhu Z;Chen S;Wang Y;Gu H
除了众所周知的过敏反应功能外，肥大细胞作为肿瘤微环境中存在的关键免疫细胞之一，在癌症进展中发挥着重要作用。然而，肥大细胞在乳腺癌发生和转移中的功能作用尚不清楚。为了测试肥大细胞在乳腺癌中的作用，我们通过将众所周知的肥大细胞缺陷小鼠品系sash (KitW-sh/W-sh)与乳腺肿瘤转基因小鼠品系MMTV-Polyoma Middle T抗原(PyMT)杂交，研究了肥大细胞缺失对乳腺肿瘤发展的影响。虽然在没有肥大细胞的情况下乳腺肿瘤的发生不受影响，但与 PyMT/野生型小鼠 (WT) 相比，PyMT/KitW-sh/W-sh 小鼠的乳腺生长和转移减少。组织学和免疫荧光分析表明，与 MMTV-PyMT/WT 小鼠相比，PyMT/KitW-sh/W-sh 小鼠的肿瘤表现出很大程度上分化的形态，血管生成减少。我们的结果表明肥大细胞可能促进乳腺癌的生长和转移。可以阻止肥大细胞生长的药物是治疗转移性乳腺癌的潜在新疗法。
Besides its well‐known function in allergic response, mast cell, one of the key immune cells present in tumor microenvironment, plays important roles in cancer progression. However, the functional role of mast cells in breast cancer development and metastasis is not well understood. To test the involvement of mast cells in breast cancer, we examined the effects of loss of mast cells on mammary tumor development by crossing the well‐known mast cell deficient mouse strain sash (KitW‐sh/W‐sh) with the mammary tumor transgenic mouse strain MMTV‐Polyoma Middle T antigen (PyMT). Although mammary tumor onset was not affected in the absence of mast cells, mammary growth and metastasis were reduced in PyMT/KitW‐sh/W‐sh mice compared with PyMT/wild‐type mice (WT). Histological and immunofluorescent analyses showed that tumors from PyMT/KitW‐sh/W‐sh mice showed largely differentiated morphology with reduced angiogenesis compared with MMTV‐PyMT/WT mice. Our results suggest that mast cells may promote breast cancer growth and metastasis. Agents that can block mast cells growth are potential new therapies to treat metastatic breast cancer.