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Mammary tumor growth and metastasis are reduced in c‐Kit mutant Sash mice

机译:c‐Kit突变型Sash小鼠的乳腺肿瘤生长和转移减少

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摘要

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.
机译:肥大细胞是肿瘤微环境中存在的关键免疫细胞之一,除了其在变态反应中的众所周知的功能外,在癌症进展中也起着重要作用。然而,肥大细胞在乳腺癌的发展和转移中的功能作用还没有被很好地理解。为了测试肥大细胞在乳腺癌中的参与,我们通过跨越著名的肥大细胞缺陷小鼠品系窗框(Kit W‐sh / W‐sh )与乳腺肿瘤转基因小鼠品系MMTV-Polyoma Middle T抗原(PyMT)。尽管在不存在肥大细胞的情况下,乳腺肿瘤的发作没有受到影响,但与PyMT /野生型小鼠(WT)相比,PyMT / Kit W‐sh / W‐sh 小鼠的乳腺生长和转移减少了。组织学和免疫荧光分析表明,与MMTV-PyMT / WT小鼠相比,PyMT / Kit W‐sh / W‐sh 小鼠的肿瘤表现出很大的分化形态,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。

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