Mena invasive (Mena(INV)) promotes multicellular streaming motility and transendothelial migration in a mouse model of breast cancer

Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Journal of Cell Science (Impact Factor: 5.43). 07/2011; 124(Pt 13):2120-31. DOI: 10.1242/jcs.086231
Source: PubMed


We have shown previously that distinct Mena isoforms are expressed in invasive and migratory tumor cells in vivo and that the invasion isoform (Mena(INV)) potentiates carcinoma cell metastasis in murine models of breast cancer. However, the specific step of metastatic progression affected by this isoform and the effects on metastasis of the Mena11a isoform, expressed in primary tumor cells, are largely unknown. Here, we provide evidence that elevated Mena(INV) increases coordinated streaming motility, and enhances transendothelial migration and intravasation of tumor cells. We demonstrate that promotion of these early stages of metastasis by Mena(INV) is dependent on a macrophage-tumor cell paracrine loop. Our studies also show that increased Mena11a expression correlates with decreased expression of colony-stimulating factor 1 and a dramatically decreased ability to participate in paracrine-mediated invasion and intravasation. Our results illustrate the importance of paracrine-mediated cell streaming and intravasation on tumor cell dissemination, and demonstrate that the relative abundance of Mena(INV) and Mena11a helps to regulate these key stages of metastatic progression in breast cancer cells.

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Available from: Bojana Gligorijevic, Apr 30, 2014
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    • "The relative abundance of MENAINV and MENA11a seems to be important to regulate key stages of the metastatic cascade in breast cancer cells. Thus, high levels of MENAINV enhance coordinated motility, transendothelial migration, and intravasation of tumor cells, promoting spontaneous lung metastases in a murine model of breast cancer [105, 106]. In contrast, increased expression of MENA11a correlates with decreased invasion, intravasation, and dissemination of cancer cells [106]. "
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    • "The decreased in vivo cell invasion observed in WASp À/À mice despite the presence of exogenous EGF supplied through the microneedle (Figure 3C) may appear to contradict the in vitro data indicating that EGF alone restored breast carcinoma cell invasion (Figure 4C). However, efficient chemotaxis in the tumor requires the propagation of chemotactic signals from cell to cell in a streaming fashion (Roussos et al., 2011; Sharma et al., 2012) so as to maintain the migration of cells. Consistent with this, blockade of CSF-1R in the presence of EGF was equally effective as EGFR blockade in reducing the number of invasive cells collected (Wyckoff et al., 2004). "
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    • "Similar to ESRPs and Rbfox2, hnRNP A1 knockdown increased skipping of ENAH/MENA exon 11, whereas increased exon 16 inclusion of SCRIB pre-mRNA (Panel B Supplementary Figure S3). Notably, splicing of exon 11A of ENAH/MENA gene has been shown to play a role in the EMT and to affect cellular motility and invasion (60,61). Notably, hnRNP A2/B1 overexpression did not affect the inclusion of exon 11A (13), suggesting that the effect of hnRNP A1 is not mediated by hnRNP A2/B1. "
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