Invasive breast carcinoma cells from patients exhibit MenaINV-and macrophage-dependent transendothelial migration

Jeanine Pignatelli, Sumanta Goswami, Joan G. Jones, Thomas E. Rohan, Evan Pieri, Xiaoming Chen, Esther Adler, Dianne Cox, Sara Maleki, Anne R. Bresnick, Frank B. Gertler, John S. Condeelis, Maja H. Oktay

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Metastasis is a complex,multistep process of cancer progression that has few treatment options. A critical event is the invasion of cancer cells into blood vessels (intravasation), through which cancer cells disseminate to distant organs. Breast cancer cells with increased abundance of Mena [an epidermal growth factor (EGF)-responsive cellmigration protein] are present withmacrophages at sites of intravasation, called TMEM sites (for tumor microenvironment of metastasis), in patient tumor samples. Furthermore, the density of these intravasation sites correlates with metastatic risk in patients. We found that intravasation of breast cancer cells may be prevented by blocking the signaling between cancer cells and macrophages. We obtained invasive breast ductal carcinoma cells of various subtypes by fine-needle aspiration (FNA) biopsies from patients and found that, in an in vitro transendothelial migration assay, cells that migrated through a layer of human endothelial cells were enriched for the transcript encoding MenaINV, an invasive isoform of Mena. This enhanced transendothelial migration required macrophages and occurred with all of the breast cancer subtypes. Using mouse macrophages and the human cancer cells from the FNAs, we identified paracrine and autocrine activation of colony-stimulating factor-1 receptor (CSF-1R). The paracrine or autocrine nature of the signal depended on the breast cancer cell subtype. Knocking down MenaINV or adding an antibody that blocks CSF-1R function prevented transendothelial migration. Our findings indicate that MenaINV and TMEM frequency are correlated prognostic markers and CSF-1 and MenaINV may be therapeutic targets to prevent metastasis of multiple breast cancer subtypes.

Original languageEnglish (US)
Article numberra112
JournalScience Signaling
Volume7
Issue number353
DOIs
StatePublished - Nov 25 2014

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Transendothelial and Transepithelial Migration
Macrophages
Cells
Breast Neoplasms
Macrophage Colony-Stimulating Factor
Colony-Stimulating Factor Receptors
Neoplasms
Neoplasm Metastasis
Tumors
Carcinoma, Ductal, Breast
Biopsy
Endothelial cells
Blood vessels
Tumor Microenvironment
Epidermal Growth Factor
Needles
Fine Needle Biopsy
Assays
Protein Isoforms
Blood Vessels

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Invasive breast carcinoma cells from patients exhibit MenaINV-and macrophage-dependent transendothelial migration. / Pignatelli, Jeanine; Goswami, Sumanta; Jones, Joan G.; Rohan, Thomas E.; Pieri, Evan; Chen, Xiaoming; Adler, Esther; Cox, Dianne; Maleki, Sara; Bresnick, Anne R.; Gertler, Frank B.; Condeelis, John S.; Oktay, Maja H.

In: Science Signaling, Vol. 7, No. 353, ra112, 25.11.2014.

Research output: Contribution to journalArticle

Pignatelli, Jeanine ; Goswami, Sumanta ; Jones, Joan G. ; Rohan, Thomas E. ; Pieri, Evan ; Chen, Xiaoming ; Adler, Esther ; Cox, Dianne ; Maleki, Sara ; Bresnick, Anne R. ; Gertler, Frank B. ; Condeelis, John S. ; Oktay, Maja H. / Invasive breast carcinoma cells from patients exhibit MenaINV-and macrophage-dependent transendothelial migration. In: Science Signaling. 2014 ; Vol. 7, No. 353.
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