Monday, March 26, 2007

Chemokines and metastasis

I read a few published papers that carried out an invasive assay, known as the matrigel assay for tumor cells (Wurfel et al, 1999). I realized one weakness - the failure to consider the role of chemokines in metastasis. Chemokines have been shown to be involved in metastasis (Muller et al, 2001). Chemokines can induce chemotaxis in metastatic tumor cells, and allow them to invade other organs. Indeed, the chemokine SDF-1 together with its associated receptor, CXCR4, are involved in the trafficking of normal stem cells and cancer stem cells, which has metastatic potential (Kucia et al, 2005).
In the absence of chemokines from the matrigel, some tumor cells may not migrate. Thus, I believe it may be a little bit premature to conclude that the non-migrating tumor cells have no or little metastatic potential. Perhaps, considerations can be made to coat the matrigel pores with chemokines to mimic physiological conditions.
Chemokines play an important role in cancer biology. Indeed, there is a focus on chemokine antagonists in cancer therapy now (Yan et al, 2006).
Citations
1) Wurfel J, Rosel M, Seiter S, Claas C, Herlevsen M, Weth R, Zoller M. Metastasis-association of the rat ortholog of the human epithelial glycoprotein antigen EGP314. Oncogene. 1999 Apr 8;18(14):2323-34.
2) Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001 Mar 1;410(6824):50-6.
3) Kucia M, Reca R, Miekus K, Wanzeck J, Wojakowski W, Janowska-Wieczorek A, Ratajczak J, Ratajczak MZ. Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells. 2005 Aug;23(7):879-94.
4) Yan L, Anderson GM, DeWitte M, Nakada MT. Therapeutic potential of cytokine and chemokine antagonists in cancer therapy. Eur J Cancer. 2006 Apr;42(6):793-802.

1 comment:

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