Process Of Metastasis Explained By 'Chase And Run' Cell Movement Mechanism

Main Category: Cancer / Oncology
Article Date: 18 Jun 2013 - 1:00 PDT Current ratings for:
Process Of Metastasis Explained By 'Chase And Run' Cell Movement Mechanism

A mechanism that cells use to group together and move around the body - called 'chase and run' - has been described for the first time by scientists at UCL.

Published in Nature Cell Biology, the new study focuses on the process that occurs when cancer cells interact with healthy cells in order to migrate around the body during metastasis. Scientists know that cancer cells recruit healthy cells and use them to travel long distances, but how this process takes place and how it could be controlled to design new therapies against cancer remains unknown.

Now, using embryonic cells called 'neural crest cells' (which are similar to cancer cells in terms of their invasive behaviour) and placode cells which are the precursors for cranial nerves (the equivalent to healthy cells) researchers at UCL have started to unravel this process.

They have found that when neural crest cells are put next to placode cells they undergo a dramatic transformation and start 'chasing' the placode cells. At the same time placode cells exhibite 'escape' behaviour when contacted by neural crest cells. The chasing behavior depends on the production of small chemical molecules by the placode cells that attracts neural crest cells toward them.

The authors of the study are confident that the process whereby cancer cells attached to healthy cells in order to migrate around the body is comparable. Healthy cells of the body try to escape from tumor cells, but are followed by malignant cells because the healthy cells produce an attractant for the cancer cells.

Dr Roberto Mayor, UCL Department of Cell and Developmental Biology and lead author of the research, said, "We use the analogy of the donkey and the carrot to explain this behaviour: the donkey follows the carrot, but the carrot moves away when approached by the donkey. Similarly the neural crest cells follow the placode cells, but placode cells move away when touched by neural crest cells."

"The findings suggest an alternative way in which cancer treatments might work in the future if therapies can be targeted at the process of interaction between malignant and healthy cells to stop cancer cells from spreading and causing secondary tumours."

"Most cancer deaths are not due to the formation of the primary tumor, instead people die from secondary tumors originating from the first malignant cells, which are able to travel and colonize vital organs of the body such as the lungs or the brain."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. The work was funded by the Medical Research Council and the Wellcome Trust.
'Chase-and-run between adjacent cell populations promotes directional collective migration' is published in the journal Nature Cell Biology.
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Cancer Metastasis Promoted By Tumor-Activated Protein

Main Category: Cancer / Oncology
Article Date: 15 May 2013 - 1:00 PDT Current ratings for:
Cancer Metastasis Promoted By Tumor-Activated Protein

Researchers at the University of California, San Diego School of Medicine and UC San Diego Moores Cancer Center report that cancers physically alter cells in the lymphatic system - a network of vessels that transports and stores immune cells throughout the body - to promote the spread of disease, a process called metastasis.

The findings are published in this week's online Early Edition of the Proceedings of the National Academy of Sciences.

Roughly 90 percent of all cancer deaths are due to metastasis - the disease spreading from the original tumor site to multiple, distant tissues and finally overwhelming the patient's body. Lymph vessels are often the path of transmission, with circulating tumor cells lodging in the lymph nodes - organs distributed throughout the body that act as immune system garrisons and traps for pathogens and foreign particles.

The researchers, led by principal investigator Judith A. Varner, PhD, professor of medicine at UC San Diego Moores Cancer Center, found that a protein growth factor expressed by tumors called VEGF-C activates a receptor called integrin α4β1 on lymphatic vessels in lymph node tissues, making them more attractive and sticky to metastatic tumor cells.

"One of the most significant features of this work is that it highlights the way that tumors can have long-range effects on other parts of the body, which can then impact tumor metastasis or growth," said Varner.

Varner said α4β1 could prove to be a valuable biomarker for measuring cancer risk, since increased levels of the activated protein in lymph tissues is an indirect indicator that an undetected tumor may be nearby.

She said whole-body imaging scans of the lymphatic network might identify problem areas relatively quickly and effectively. "The idea is that a radiolabeled or otherwise labeled anti-integrin α4β1 antibody could be injected into the lymphatic circulation, and it would only bind to and highlight the lymphatic vessels that have been activated by the presence of a tumor."

Varner noted that α4β1 levels correlate with metastasis - the higher the level, the greater the chance of the cancer spreading. With additional research and clinical studies, doctors could refine treatment protocols so that patients at higher risk are treated appropriately, but patients at lower or no risk of metastasis are not over-treated.

The researchers noted in their studies that it is possible to suppress tumor metastasis by reducing growth factor levels or by blocking activation of the α4β1 receptor. Varner said an antibody to VEGF-R3 is currently in Phase 1 clinical trials. An approved humanized anti-α4β1 antibody is currently approved for the treatment of multiple sclerosis and Crohn's disease. Varner said her lab at UC San Diego Moores Cancer Center is investigating the possibility of developing one for treating cancer.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. Co-authors include Barbara Garmy-Susini, Christie J. Avraamides, Michael C. Schmid and Philippe Foubert, UC San Diego Moores Cancer Center; Jay S. Desgrosellier, UC San Diego Moores Cancer Center and UCSD Department of Pathology; Lesley G. Ellies, Scott R. Vanderberg, Brian Datnow, Huan-You Wang and David A. Cheresh, UCSD Department of Pathology; Andrew M. Lowy and Sarah L. Blair, UC San Diego Moores Cancer Center and UCSD Department of Surgery.
Funding for this research came, in part, from National Institutes of Health grants CA83133 and CA126820; Department of Defense grant W81XWH-06-1-052 and NIH-National Cancer Institute grant U54 CA119335.
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Study Suggests Cutaneous Squamous Cell Carcinoma Carries Risk Of Metastasis And Death

Main Category: Cancer / Oncology
Also Included In: Dermatology
Article Date: 17 May 2013 - 2:00 PDT Current ratings for:
Study Suggests Cutaneous Squamous Cell Carcinoma Carries Risk Of Metastasis And Death

JAMA Dermatology Study Highlights

A study by Chrysalyne D. Schmults, M.D., M.S.C.E., of Brigham and Women's Hospital, Boston, and colleagues suggests cutaneous squamous cell carcinoma (CSCC) carries a low but significant risk of metastasis and death.

The ten-year retrospective cohort study was conducted at an academic medical center in Boston, and included 985 patients with 1,832 tumors. Main measures of the study were subhazard ratios for local recurrence, nodal metastasis, disease-specific death, and all-cause death adjusted for presence of known prognostic risk factors. The median follow-up was 50 months.

Local recurrence occurred in 45 patients (4.6 percent) during the study period; 36 (3.7 percent) developed nodal metastases; and 21 (2.1 percent) died of CSCC. Independent predictors for nodal metastasis and disease-specific death were tumor diameter of at least 2 centimeters, poor differentiation, invasion beyond fat, and ear or temple location. Perineural invasion, cancer spreading to the space surround a nerve, was also associated with disease-specific death, as was anogenital location. Overall death was associated with poor differentiation and invasion beyond fat, the study finds.

"Tumor diameter of at least 2 centimeters, invasion beyond fat, poor cellular differentiation, perineural invasion, and ear, temple, or anogenital location were risk factors for poor outcomes. These 5 risk factors may be among the most significant drivers of CSCC outcomes, but further studies are needed to replicate our findings" the authors conclude.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. JAMA Dermatol. Published May 15, 2013. 2013;149(5):541-547. Please use one of the following formats to cite this article in your essay, paper or report:

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