Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
PURITAN MEDICAL
GLOBETECH PUBLISHING LLC

Inhibition of a Tyrosine Kinase in Mouse Models Decreased Tumor Growth and Metastasis

By BiotechDaily International staff writers
Posted on 24 Jul 2013
Studies with genetically engineered mouse models of breast cancer, melanoma, and colon cancer have shown that inhibiting the action of the tyrosine kinase MerTK (c-mer proto-oncogene tyrosine kinase) increased the ability of the animals to produce an active immune response and blocked tumor growth and metastasis.

Investigators at the University of North Carolina (Chapel Hill, USA) transplanted tumors into normal mice and into mice that had been genetically engineered to lack the gene for MerTK. MerTK is a member of a receptor tyrosine kinase (RTK) family that also includes AXL and TYRO3. This enzyme is expressed in noncancerous cells found in the tumor microenvironment. It is also ectopically expressed or overexpressed in many hematological and epithelial malignant cells. Expression of MerTK correlates with poor prognosis or chemoresistance in some human tumor types.

Results published in the July 8, 2013, online edition of the Journal of Clinical Investigation revealed that tumors grew slowly and were poorly metastatic in mice lacking the MerTK gene. Transplantation of bone marrow from mice lacking MerTK, but not wild-type bone marrow, into lethally irradiated MMTV-PyVmT mice (a model of metastatic breast cancer) decreased tumor growth and altered cytokine production by tumor CD11b+ cells. Although MerTK expression was not required for tumor infiltration by leukocytes, leukocytes from animals lacking MerTK exhibited lower tumor cell–induced expression of wound healing cytokines and enhanced expression of acute inflammatory cytokines.

These finds show that MerTK signaling promoted tumor growth by dampening acute inflammatory cytokines while inducing wound healing cytokines. These results suggest that inhibition of MerTK in the tumor microenvironment may have clinical benefit, stimulating antitumor immune responses or enhancing immunotherapeutic strategies.

“Our work strongly indicates that if you could inhibit MerTK signaling in the tumor bed, you could trigger a more active immune system leading to a stronger T-cell killing response against the tumor,” said senior author Dr. Shelton Earp, professor of pharmacology and medicine at the University of North Carolina. “We hope to create a new, more MerTK selective tool with which to stimulate the initial tumor response and combine this strategy with existing drugs that extend the immune response. If we can initiate a stronger response and sustain that activity, we may be more effective in treating metastatic cancer. Tumor cells can move throughout the body thwarting some of our best therapeutic interventions. The immune system is mobile and may be able to help eliminate tumor cells even at distant sites.”

Related Links:

University of North Carolina




Channels

Drug Discovery

view channel
Image: A new micelle delivery system for the protective polyphenols resveratrol and quercetin (mRQ) may have value in cancer chemotherapy (Photo courtesy of Oregon State University).

Micelles Containing Resveratrol and Quercetin Reverse Doxorubicin Cardiotoxicity

Cancer researchers blocked the toxic effects of the cancer drug doxorubicin (DOX) by administering it together with the plant antioxidants resveratrol and quercetin. Although in use for more than 40... Read more

Lab Technologies

view channel
Image: The Leica DM2500 LED Microscope for clinical laboratories and research applications (Photo courtesy of Leica Microsystems).

New LED Microscope Completes Line of Clinical and Research Tools

A popular microscope used for both clinical and research applications is now available with LED illumination. The Leica (Wetzlar, Germany) DM2500 and DM2500 LED microscopes represent a class of tools... Read more

Business

view channel

Teva Buys Allergan Generic Business Unit

Teva Pharmaceutical Industries (Petah Tikva, Israel) has bought the Allergan (Irvine, CA, USA) generic drugs business for USD 40.5 billion in cash and stock, solidifying its position as the world's largest generic drug maker. Under the terms of the agreement, Teva will pay USD 33.75 billion in cash and USD 6.... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.