LONDON—Cancer metastasis remains one of the biggest issuesthat drug developers face in targeting the disease. While countless effectiveoptions exist for treating the variety of cancer types that exist, there isalways the concern of treating tumors before they have the chance to spread.Generally such efforts have focused on destroying existing tumors before theycan metastasize to other sites in the body, but a group of researchers fromCancer Research UK are taking a different tack: learning more about how cancersmove in order to slow or halt their movement itself.
The scientists, led by Erik Sahai and Paul Bates, havedeveloped a computer model based on melanoma skin cancer cells that can predicthow a cancer cell might move in different instances. Two of the possible typesof movement are crawling or squeezing, and their usage varies depending on theenvironment they are trying to invade. On a flat surface, cancer cells werefound to crawl along, while in a webbed environment, they will often becomerounder to squeeze through gaps.
"For cancer to spread, cancer cells actually need to moveinside the body, from one point to another, stop and start a new tumor," saidDr. Melda Tozluoglu, lead author of the study. "Our work focuses onunderstanding how the cancer cells move in the body so that we can hamstringthem—lock them into place so that other treatments can destroy them.
"Our study shows that cancer cells need different molecularmechanisms to navigate in different environments, just like you would needlight running shoes to jog in the park but strong books to hike in hills in therain. We also know that cancer cells have the ability to use all differentmethods of movement, so stopping just one route will not stop them spreadingthroughout the body. In other words, if we take their hiking boots away, theywill switch to running shoes, and, although they may not be as fast, they willkeep moving. This means we need to use drugs that target the many differenttype of movement that cancer cells can take advantage of."
Sahai notes that their group has been working on thisresearch since the team began in 2004, and their research isn't limited to skincancer.
"Although the paper is focused on a melanoma cell line, weprovide supporting data in a breast cancer model and primary human squamouscell carcinoma explants," says Sahai. "More broadly, amoeboid-squeezingmigration of cancer cells has been reported in breast cancer and fibrosarcomamodels by John Condeelis and Peter Friedl."
The type of cell movement displayed depends on both the typeof cancer in question and the environment that the cells are trying to invade,but Sahai says "the environment could almost be considered 'dominant,'" notingthat the most dangerous cells are generally the ones that are "best able toadapt their mode of migration to their environment."
As for what kinds of drugs or treatments might serve to haltcancer cell movement, Sahai notes that "plasticity is likely to be a problem,"and combination strategies might be the best approach. Sahai says theircomputer model will be helpful in "predicting non-trivial results of drugcombinations," and as they move forward, the team will be incorporatingmultiple cells and matrix degradation.
"Stopping cancers from spreading to new parts of the body inan important aim of our researchers, and it's essential for making treatmentsmore effective," Dr. Julie Sharp, senior science information manager at CancerResearch UK, said in a press release. "Research like this, which benefits ourunderstanding of all types of cancer, will be central to the work at theFrancis Crick Institute, a new super-laboratory in London headed by Prof. SirPaul Nurse, where scientists will tackle major diseases such as cancer usingthe very latest technologies."