Metastasis causes most cancer-related deaths, and one poorly understood aspect of metastatic cancer is the adaptability of cells from a primary tumor to create new niches and survive in multiple, different secondary sites. We used quantitative mass spectrometry to analyze the extracellular matrix (ECM), a critical component of metastatic niches, in metastases to the brain, lungs, liver, and bone marrow, all derived from parental MDA-MB-231 triple-negative breast cancer cells. Tumor and stromal cells cooperated in forming niches; stromal cells produced predominantly core, structural ECM proteins and tumor cells produced a diverse array of ECM-associated proteins, including secreted factors and modulators of the matrix. In addition, tumor and stromal cells together created distinct niches in each tissue. Downregulation of SERPINB1, a protein elevated in brain metastases, led to a reduction in brain metastasis, suggesting that some niche-specific ECM proteins may be involved in metastatic tropism. SIGNIFICANCE: Tumor and stromal cells together create distinct ECM niches in breast cancer metastases to various tissues, providing new insight into how tumor cells adapt to survive in different tissue environments.

中文翻译：

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不同器官异种移植乳腺癌转移的 ECM 的蛋白质组学分析揭示了不同的转移性位点。

转移会导致大多数与癌症相关的死亡，而对转移性癌症知之甚少的一个方面是原发肿瘤细胞的适应性，以创造新的生态位并在多个不同的继发部位存活。我们使用定量质谱来分析细胞外基质 (ECM)，这是转移性生态位的关键组成部分，在脑、肺、肝和骨髓的转移中，所有这些都来自亲本 MDA-MB-231 三阴性乳腺癌细胞. 肿瘤和基质细胞合作形成生态位；基质细胞主要产生核心、结构性 ECM 蛋白，而肿瘤细胞产生多种 ECM 相关蛋白，包括基质的分泌因子和调节剂。此外，肿瘤和基质细胞共同在每个组织中创造了不同的生态位。SERPINB1 的下调，一种在脑转移灶中升高的蛋白质导致脑转移减少，这表明某些生态位特异性 ECM 蛋白可能与转移趋向性有关。意义：肿瘤和基质细胞共同在乳腺癌转移到各种组织中创造了不同的 ECM 生态位，为了解肿瘤细胞如何适应不同组织环境中的生存提供了新的见解。