TGFβ primes breast tumors for lung metastasis seeding through angiopoietin-like 4 Journal Article
| Authors: | Padua, D.; Zhang, X. H. F.; Wang, Q.; Nadal, C.; Gerald, W. L.; Gomis, R. R.; Massague, J. |
| Article Title: | TGFβ primes breast tumors for lung metastasis seeding through angiopoietin-like 4 |
| Abstract: | Cells released from primary tumors seed metastases to specific organs by a nonrandom process, implying the involvement of biologically selective mechanisms. Based on clinical, functional, and molecular evidence, we show that the cytokine TGFβ in the breast tumor microenvironment primes cancer cells for metastasis to the lungs. Central to this process is the induction of angiopoietin-like 4 (ANGPTL4) by TGFβ via the Smad signaling pathway. TGFβ induction of Angptl4 in cancer cells that are about to enter the circulation enhances their subsequent retention in the lungs, but not in the bone. Tumor cell-derived Angptl4 disrupts vascular endothelial cell-cell junctions, increases the permeability of lung capillaries, and facilitates the trans-endothelial passage of tumor cells. These results suggest a mechanism for metastasis whereby a cytokine in the primary tumor microenvironment induces the expression of another cytokine in departing tumor cells, empowering these cells to disrupt lung capillary walls and seed pulmonary metastases. © 2008 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; cancer survival; controlled study; intercellular signaling peptides and proteins; unclassified drug; human cell; histopathology; nonhuman; bone metastasis; mouse; animal; cytology; metabolism; mouse mutant; animals; mice; animal tissue; metastasis; breast cancer; gene expression; gene expression profiling; signaling; smad protein; transforming growth factor beta; lung neoplasms; animal experiment; animal model; cell motion; cancer cell culture; pathology; mice, scid; tumor cells, cultured; cell line, tumor; breast neoplasms; endothelium cell; endothelial cells; lung tumor; lung metastasis; statistical analysis; xenograft; cell culture; oligonucleotide array sequence analysis; signal peptide; breast tumor; tumor cell line; neoplasms, experimental; transplantation, heterologous; cell migration; cell movement; cellbio; dna microarray; experimental neoplasm; neoplasm transplantation; cell junction; mice, inbred nod; bioinformatics; nonobese diabetic mouse; intercellular junctions; scid mouse; humdisease; cancer transplantation; angiopoietin; capillary permeability; angiopoietin like 4; smad anchor for receptor activation; angptl4 protein, human |
| Journal Title: | Cell |
| Volume: | 133 |
| Issue: | 1 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2008-04-04 |
| Start Page: | 66 |
| End Page: | 77 |
| Language: | English |
| DOI: | 10.1016/j.cell.2008.01.046 |
| PUBMED: | 18394990 |
| PROVIDER: | scopus |
| PMCID: | PMC2390892 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 147" - "Export Date: 17 November 2011" - "CODEN: CELLB" - "Source: Scopus" |
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