Decoy protein shows promise as potential cancer therapy

July 19, 2004

Two research studies published in the July issue of Cancer Cell demonstrate that targeting a portion of a protein associated with many human cancers, including breast, lung, liver, kidney, and colorectal cancers, may have significant potential therapeutic applications with less toxicity than more general inhibitors of the same signaling pathway.

Fundamental processes like cell proliferation, migration, differentiation, and survival are regulated in part by hepatocyte growth factor (HGF). HGF controls and coordinates many events that are critical for embryonic development and for adult wound healing and tissue regeneration. However, in addition to playing a necessary role in these essential normal processes, HGF signaling through its receptor Met is usurped by many tumors to promote growth, survival, and metastases.

Dr. Paolo Michieli and colleagues from the University of Torino Medical School in Italy examined whether targeted inhibition of HGF/Met signaling may be an effective anticancer therapeutic. The researchers engineered a truncated version of the Met receptor that consisted only of the receptor's extracellular domain. This version of Met, called decoy Met, was soluble and could be systemically introduced into mice. Decoy Met inhibited the growth and survival of a variety of human tumor cells that were grafted into mice, interfered with the ability of the tumors to establish a blood supply, and prevented the tumor cells from spreading. Importantly, decoy Met did not interfere with normal physiological functions in adult mice. The authors suggest that the extracellular portion of the receptor present in decoy Met successfully competes for HGF binding and may be a promising therapeutic agent.

A second study by Dr. Dineli Wickramasinghe and colleagues from the Department of Molecular Oncology at Genentech in San Francisco examined a very specific part of the extracellular domain of the Met receptor, called the Sema domain. The Met Sema domain was required for HGF-stimulated Met activation in tumor cells. In addition, the Met receptor dimerization, a process that is necessary for full activation of Met and therefore activation of signaling molecules downstream of Met, only occurred when the Sema domain was intact. This is significant because hyperactivation of the Met receptor, even in the absence of HGF, is common in many types of cancer.

When the Sema domain by itself was introduced into Met-overexpressing tumor cells, it blocked receptor activation and downstream signals that stimulate cell motility and migration. According to Dr. Wickramasinghe, "These observations point to the exciting prospect of treating Met-overexpressing tumors not only by targeting the Sema domain of Met but also by utilizing the Sema domain itself as a biotherapeutic."
-end-
P. Michieli, M. Mazzone, C. Basilico, S. Cavassa, A. Sottile, L. Naldini, and P.M. Comoglio: "Targeting the tumor and its microenvironment by a dual-function decoy Met receptor"

M. Kong-Beltran, J. Stamos, and D. Wickramasinghe: "The Sema domain of Met is necessary for receptor dimerization and activation"

Related Preview by Y.-W. Zhang, C. Graveel, N. Shinomiya, and G.F. Vande Woude: "Met decoys: Will cancer take the bait?"

Publishing in Cancer Cell, Volume 6, Number 1, July 2004.

Cell Press

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.