Direct Signaling Between Platelets and Cancer Cells Induces an Epithelial-Mesenchymal-Like Transition and Promotes Metastasis

By Myriam Labelle, Shahinoor Begum, R. Hynes. Cancer Cell, 2011

1,784 citations recorded by the source corpus.

SUMMARY Interactions of cancer cells with the primary tumor microenvironment are important determinants of cancer progression towards metastasis but it is unknown whether additional prometastatic signals are provided during the intravascular transit to the site of metastasis. Here, we show that platelet-tumor cell interactions are sufficient to prime tumor cells for subsequent metastasis. Platelet-derived TGFβ and direct platelet-tumor cell contacts synergistically activate the TGFβ/Smad and NF-κB pathways in cancer cells, resulting in their transition to an invasive mesenchymal-like phenotype and enhanced metastasis in vivo. Inhibition of NF-κB signaling in cancer cells or ablation of TGFβ1 expression solely in platelets protects against lung metastasis in vivo. Thus, cancer cells rely on platelet-derived signals outside of the primary tumor for efficient metastasis.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/4dee588730f1a173a48cab5f5bd4b64acd4d46a9

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Citations in the corpus

EMERGING BIOLOGICAL PRINCIPLES OF METASTASIS (2017, neutral): “Notably, TGF-β secreted by degranulating platelets can act in coordination with contact-dependent signals that activate the NF-κB pathway in carcinoma cells, thereby inducing or sustaining the expression of EMT programs in the CTCs (Labelle et al., 2011).”
Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance (2019, background): “Plateletderived TGF-β and direct platelet-tumor cell contact synergistically activate the TGF-β/ Smad and NF-κB pathways in cancer cells, increasing their invasive ability and thus favoring extravasation (Labelle et al., 2011).”
Epithelial-Mesenchymal Plasticity: A central regulator of cancer progression (2015, background): “, 2014), and TGF-β is released from myofibroblasts and platelets (Labelle et al., 2011).”
Epithelial–mesenchymal plasticity in carcinoma metastasis (2013, background): “Together, these studies suggest that successful metastasis may depend on the maintenance of a mesenchymal state in CTCs.”
Dependency of colorectal cancer on a TGF-beta-driven programme in stromal cells for metastasis initiation (2012, background): “In addition, platelets are a rich source of TGF-b (Labelle et al., 2011).”
Circulating Tumor Cell Clusters are Oligoclonal Precursors of Breast Cancer Metastasis (2014, background): “We therefore cannot exclude additional contributions from nonmalignant cells within larger microemboli (Duda et al., 2010; Labelle et al., 2011; Stott et al., 2010), including potential stromal-derived tropism signals (Zhang et al., 2013).”
Metastatic Stem Cells: Sources, Niches, and Vital Pathways (2014, background): “What prompts these cells to respond to TGF-b with an EMT right before extravasation (Labelle et al., 2011) and with MET right after is unknown.”
The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis (2022, background): “By expressing thrombin, MCSCs can bind to coagulation factors on platelets upon entry into the circulation, forming a unique immune mechanism to protect metastatic cells from immune escape and maintaining mesenchymal properties by activating the SMAD and Notch pathways [174, 175].”
Circulating Platelets as Mediators of Immunity, Inflammation and Thrombosis (2018, methodology): “In vivo studies eliminating TGF-β specifically from platelets have proposed that this cytokine, when originating from platelets, is solely responsible for inducing an invasive epithelial–mesenchymal transition to metastasis.(27) These studies used the PF4Cre murine model which, at the time, was beli”
Accessories to the crime: functions of cells recruited to the tumor microenvironment. (2012, neutral): “A recent report solidified these suspicions (Labelle et al., 2011), revealing that platelets induce a transitory EMT by physically associating with blood-borne cancer cells, facilitating extravasation and seeding of metastases.”
Platelet secretion: From haemostasis to wound healing and beyond (2015, background): “permissive factor for metastasis, specifically in epithelial–mesenchymal-like transition [108].”