Prof. Insall: The principal message is that melanoma cells make their own steering signals, and thus drive themselves out of the tumour and into the bloodstream. This comes in two parts:
(a) The principal steering signal when we assay melanoma spread in vitro is lysophosphatidic acid, LPA. LPA steers cells with really remarkable accuracy; blocking LPA receptors stops them from spreading without hurting their health or ability to move.
(b) Where does the LPA gradient come from? They make it themselves. There seems to be lots of LPA around; they break down the LPA near them, leading to a gradient that’s low near the cells and high further away. This is the gradient that steers the tumour cells.
Medical Research: What was most surprising about the results?
Prof. Insall: Everyone always looks for an external driver. Who is luring these tumour cells out, and why? But it turns out they make the signal themselves – because the signal is not the EXISTENCE of LPA, but the GRADIENT of LPA.
Medical Research: What should clinicians and patients take away from your report?
Prof. Insall: For clinicians: never do anything to cause inflammation near a possible melanoma, in particular a biopsy; just cut it out with a wide margin. This is (fortunately) current medical practice in most countries; now we know why. We also suspect we know why the tumour (Breslow) thickness is the most important prognostic factor – the thickness of the tumour determines its ability to create an LPA gradient.
Medical Research: What recommendations do you have for future research as a result of this study?
Prof. Insall: We have to find a way of measuring whether or not melanoma cells are experiencing an LPA gradient, as a prognostic tool. This will be tricky – but is likely to provide the best possible assessment of whether a tumour is likely to have spread.
Andrew J. Muinonen-Martin, Olivia Susanto, Qifeng Zhang, Elizabeth Smethurst, William J. Faller, Douwe M. Veltman, Gabriela Kalna,mColin Lindsay, Dorothy C. Bennett, Owen J. Sansom, Robert Herd, Robert Jones, Laura M. Machesky, et al Robert H. Insall
Published: October 14, 2014 DOI: 10.1371/journal.pbio.1001966