WCLC 2025 - Posters & ePosters-EP.02.09 Deciphering CD47-Mediated Platelet-Tumor Crosstalk and Its Role in NSCLC Metastasis

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This study investigates the role of CD47, a cell surface protein that transmits a "don't eat me" signal to immune cells, in promoting metastasis of non-small cell lung cancer (NSCLC) via interactions with platelets. CD47 is frequently overexpressed in NSCLC tumors, allowing cancer cells to evade immune destruction. Prior research has shown that inhibiting CD47 can reduce tumor growth and metastasis, making it an attractive therapeutic target.<br /><br />The research aimed to determine whether NSCLC cells use CD47 to bind platelets, thereby facilitating metastatic spread. Using CRISPR/Cas9, CD47 was knocked out (KO) in murine (LLC) and human (H1299) lung cancer cell lines. In vitro assays demonstrated that CD47 KO cells had decreased platelet binding and activation compared to wild-type (WT) cells. This suggests CD47 mediates cancer cell interaction with platelets, which are known to aid tumor cell dissemination.<br /><br />In vivo, platelet depletion did not affect metastasis of WT LLC cells, but combining CD47 KO with platelet depletion abolished lung metastasis in a mouse tail-vein injection model. This indicates that platelet interactions through CD47 are critical for metastatic progression. Bulk RNA sequencing of tumor cells from mouse models revealed that CD47 KO tumors showed downregulation of genes associated with epithelial-mesenchymal transition (EMT), coagulation, inflammatory response, and angiogenesis—processes implicated in metastasis and tumor progression.<br /><br />The study concludes that CD47 facilitates lung cancer metastasis by promoting platelet interactions and activating pro-metastatic transcriptional programs. Targeting CD47 could inhibit metastasis and tumor immune evasion, offering a promising lung cancer treatment strategy. Future work will focus on identifying platelet-activating factors secreted by cancer cells and exploring platelet depletion effects in additional NSCLC models to further elucidate these mechanisms.

Asset Subtitle

Asa Lau

Meta Tag

Speaker Asa Lau

Topic Tumor Biology – Preclinical Biology

Keywords

CD47

non-small cell lung cancer

NSCLC

platelet interaction

metastasis

CRISPR/Cas9 knockout

epithelial-mesenchymal transition

tumor immune evasion

RNA sequencing

lung cancer therapy