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Elucidation of the role of chemokine receptors in the control of lung metastasis of breast cancer cells.
Author(s) -
Biragyn Arya,
Anderson Robin L,
Olkhanud Purevdorj B
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.665.7
Subject(s) - chemokine receptor , ccr10 , ccr1 , c c chemokine receptor type 6 , ccl21 , cancer research , cc chemokine receptors , ccl13 , xcl2 , ccl7 , chemokine receptor ccr5 , biology , metastasis , chemokine , cxc chemokine receptors , microbiology and biotechnology , immunology , cancer , inflammation , genetics
Chemokines regulate trafficking of cells acting through differentially expressed chemokine receptors. They have been implicated in migration of malignant cells, although their direct role in the organ metastasis remains unresolved. The major obstacle is that chemokine receptors on tumor cells are often not detectable by use of conventional surface staining techniques. We have hypothesized that this is due to the heterogeneity of cancer cells that would “hide” a minor subset of cells that could express chemokine receptors in their mist. To associate organ metastasis with expression of chemokine receptors, the hypothetical chemokine receptor‐expressing cells were depleted using chemotoxins (chemokines that specifically kill the respective receptor‐ expressing cells). As a result, we have generated a number of 4T1 clones that only differed by the loss of expression of a particular chemokine receptor. This enabled us to also demonstrate that CCR4 is the key receptor that controls lung metastasis 4T1 cells. Thus, our data not only indicate that expression of a single chemokine receptor is sufficient to induce lung metastasis, but also clearly demonstrates that organ homing pattern is only determined by the chemokine receptor‐expressing subset of cancer cells.