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Endothelial focal adhesion kinase mediates cancer cell homing to discrete regions of the lungs via E-selectin up-regutation

机译:内皮黏着斑粘附激酶通过E-选择素上调介导癌细胞归巢到肺的离散区域

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摘要

Primary tumors secrete factors that alter the microenvironment of distant organs, rendering those organs as fertile soil for subsequent metastatic cancer cell colonization. Although the lungs are exposed to these factors ubiquitously, lung metastases usually develop as a series of discrete lesions. The underlining molecular mechanisms of the formation of these discrete lesions are not understood. Here we show that primary tumors induce formation of discrete foci of vascular hyperpermeability in premetastatic lungs. This is mediated by endothelial cell-focal adhesion kinase (FAK), which up-regulates E-selectin, leading to preferential homing of metastatic cancer cells to these foci. Suppression of endothelial-FAK or E-selectin activity attenuates the number of cancer cells homing to these foci. Thus, localized activation of endothelial FAK and E-selectin in the lung vasculature mediates the initial homing of metastatic cancer cells to specific foci in the lungs.
机译:原发性肿瘤分泌的因子会改变远处器官的微环境,使这些器官成为随后转移性癌细胞定殖的肥沃土壤。尽管肺无处不在地暴露于这些因素,但是肺转移通常发展为一系列离散的病变。这些离散损伤形成的分子机制尚不清楚。在这里,我们显示原发性肿瘤在转移前的肺中诱导血管高通透性离散灶的形成。这是由内皮细胞焦点粘附激酶(FAK)介导的,该激酶上调E-选择素,导致转移性癌细胞优先归巢于这些病灶。抑制内皮细胞FAK或E-选择素的活性会减弱归巢于这些病灶的癌细胞的数量。因此,肺血管中内皮FAK和E-选择蛋白的局部活化介导了转移性癌细胞最初归巢到肺中的特定病灶。

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    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada, Shinjyuku-ku, Tokyo 162-8666, Japan;

    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Department of Pharmacology, Tokyo Women's Medical University, Tokyo 162-8666, Japan;

    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    metastasis; permeability;

    机译:转移;渗透性;

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