Scholarlink

<p>Metastatic tumor cell dissemination is the leading cause of cancer-related deaths. Clustered circulating tumor cells (CTCs) possess higher metastatic potential than single CTCs. Epithelial adherens junction (AJ) proteins typically mediate stable cell-cell interactions; however, these proteins are frequently lost in highly aggressive triple-negative breast cancers (TNBCs), raising the question of how CTCs from such tumors cluster. Here we show that the extracellular matrix (ECM) component hyaluronan (HA) mediates AJ-independent CTC clustering in TNBCs. HA is necessary and sufficient to drive clustering of tumor cells expressing its receptor CD44. Mechanistically, HA initiates contact between neighboring cells through actin-based membrane protrusions. As cells are pulled closer, these initial interactions expand to membrane-membrane contact&#xa0;and are subsequently stabilized by desmosomes. CTC-derived HA also acts as a docking platform to&#xa0;promote heterotypic cluster formation by recruiting non-CTCs, including immune cells.&#xa0;Thus, this ECM–receptor interaction enables CTC clustering and survival under shear stress, enhancing TNBC metastasis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Extracellular matrix mediates circulating tumor cell clustering in triple-negative breast cancer metastasis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月6日

查看全文
  • Georg OM Bobkov,
  • Khushali J. Patel,
  • Bree M. Lege,
  • Rong Zheng,
  • Gad Shaulsky,
  • Matthew J. Ellis,
  • Chonghui Cheng

摘要

Metastatic tumor cell dissemination is the leading cause of cancer-related deaths. Clustered circulating tumor cells (CTCs) possess higher metastatic potential than single CTCs. Epithelial adherens junction (AJ) proteins typically mediate stable cell-cell interactions; however, these proteins are frequently lost in highly aggressive triple-negative breast cancers (TNBCs), raising the question of how CTCs from such tumors cluster. Here we show that the extracellular matrix (ECM) component hyaluronan (HA) mediates AJ-independent CTC clustering in TNBCs. HA is necessary and sufficient to drive clustering of tumor cells expressing its receptor CD44. Mechanistically, HA initiates contact between neighboring cells through actin-based membrane protrusions. As cells are pulled closer, these initial interactions expand to membrane-membrane contact and are subsequently stabilized by desmosomes. CTC-derived HA also acts as a docking platform to promote heterotypic cluster formation by recruiting non-CTCs, including immune cells. Thus, this ECM–receptor interaction enables CTC clustering and survival under shear stress, enhancing TNBC metastasis.