Posted by: Dan | May 11, 2006

RANKing Cancer Cell Metastasis

Dang – I literally had this paper, by D. Holstead Jones et al. (March 30th issue of Nature, printed out to read and blog about on my desk for about a week now, the Cell Migration Gateway beat me to it.

Oh well – go check it out for a good write-up of the article. For my (very brief) synopsis, check below the fold.

CMG also has a nice time-line of Milestones in Cancer Research.

Brief synopsis

Understanding the molecular mechanisms of why different cancers preferentially metastasize to certain organs has long been a question of interest, with the leading explanations being that the microenvironment of the primary tumor actively participates in this propensity, and/or the original tumor’s local chemokine milieu “primes” cancer cells to fertile “soils” of particular tissues.

In this study, Jones et al. focus on bone metastases, and shows that the cytokine RANKL attracts human epithelial cancer (e.g. breast cancer) cells and melanoma cells that express RANK. In both bone and mammary tissue, RANKL/RANK perform necessary and exclusive functions, without interferring with each other (normally). But following malignant transformation (or EMT), malignant cells expressing RANK may get where they don’t belong – in the bloodstream – and become recruited to a tissue with a vaguely familiar chemokine milieu.

Or maybe you prefer the CMG’s synopsis:

To study the effects of RANKL on tumour metastasis in vivo, the authors examined whether OPG-mediated inhibition of RANKL signalling altered metastasis into the bones of mice injected with B16F10 melanoma cells. While inhibition of RANKL did not alter the rate of metastasis into ovaries, brain and the adrenal glands, it did markedly reduce tumour formation in bones.

Reference

  • Regulation of cancer cell migration and bone metastasis by RANKL. Jones DH, Nakashima T, Sanchez OH, Kozieradzki I, Komarova SV, Sarosi I, Morony S, Rubin E, Sarao R, Hojilla CV, Komnenovic V, Kong YY, Schreiber M, Dixon SJ, Sims SM, Khokha R, Wada T, Penninger JM. Nature. 2006 Mar 30; 440(7084):692-6. Pubmed

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