Abstract:
:Primary tumors secrete factors that alter the microenvironment of distant organs, rendering those organs as fertile soil for subsequent metastatic cancer cell colonization. Although the lungs are exposed to these factors ubiquitously, lung metastases usually develop as a series of discrete lesions. The underlining molecular mechanisms of the formation of these discrete lesions are not understood. Here we show that primary tumors induce formation of discrete foci of vascular hyperpermeability in premetastatic lungs. This is mediated by endothelial cell-focal adhesion kinase (FAK), which up-regulates E-selectin, leading to preferential homing of metastatic cancer cells to these foci. Suppression of endothelial-FAK or E-selectin activity attenuates the number of cancer cells homing to these foci. Thus, localized activation of endothelial FAK and E-selectin in the lung vasculature mediates the initial homing of metastatic cancer cells to specific foci in the lungs.
journal_name
Proc Natl Acad Sci U S Aauthors
Hiratsuka S,Goel S,Kamoun WS,Maru Y,Fukumura D,Duda DG,Jain RKdoi
10.1073/pnas.1100446108subject
Has Abstractpub_date
2011-03-01 00:00:00pages
3725-30issue
9eissn
0027-8424issn
1091-6490pii
1100446108journal_volume
108pub_type
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