November 10, 2006

Meeting probes twists, turns of matrix biology

Featured Image

Kevin Churchwell, M.D.

Meeting probes twists, turns of matrix biology

Matrix biology could be described as the science of acronyms.

Many of the molecules known to act in the matrix — the space between cells — have tongue-twisting names that collapse into neat, sometimes humorous abbreviations.

The ADAMs family, reminiscent of one of TV's most eccentric households, refers to a group of membrane-anchored enzymes that cleave and “shed” other proteins into the matrix, where they engage in a wide variety of functions, from fertilization to blood vessel growth.

Some of their actions are not so benign. ADAMs have been implicated in cancer, asthma, Alzheimer's disease and rheumatoid arthritis. A better understanding of these pivotal enzymes could lead to new treatments, said Carl Blobel, M.D., Ph.D., senior scientist at the Hospital for Special Surgery at Weill Cornell Medical College in New York City.

Blobel was a plenary speaker last week at the biennial national meeting of the American Society for Matrix Biology in Nashville, co-hosted by the Vanderbilt Center for Matrix Biology and Vanderbilt University School of Medicine. About 400 scientists from around the world attended, making the four-day-long meeting at the Nashville Convention Center one of the largest ever co-hosted by the medical school.

Harold Moses, M.D., director emeritus of the Vanderbilt-Ingram Cancer Center, gave the keynote address Nov. 1 on the regulatory role that transforming growth factor beta (TGF-beta) plays in the interactions between the stroma and epithelium.

Moses pioneered current understanding of TGF-beta as both a cell growth stimulator (tumor promoter) and cell growth inhibitor (tumor suppressor) under different circumstances.

This crucial molecule exerts its effects not only in the epithelium, the tissue that lines the body, inside and out, and from which most cancers arise, but also in the stroma, the connective tissue framework of organs, glands and other body structures.

The complexity of these cell-cell communications within and between different tissue compartments opens up new avenues for targeted therapies, said Moses, the Hortense B. Ingram Professor of Molecular Oncology.

Billy Hudson, M.D., Ph.D., director of the Vanderbilt Center for Matrix Biology and one of the organizers of the meeting, discussed how collagens, the fibrous proteins that make up connective tissue, are assembled.

Determining how these “beautiful molecules” are assembled into fibrils, networks and other structures is a key first step to understanding their function, said Hudson, an expert on their role in diseases such as diabetes and Goodpasture syndrome, which affects the kidney.

Linda J. Sandell, Ph.D., director of research in Orthopaedic Surgery at Washington University in St. Louis, and president of the American Society for Matrix Biology, has been investigating the connection between CD-RAP and cancer.

No, CD-RAP is not a music album, but a major cartilage protein — discovered by Sandell and her colleagues — that is also synthesized by a number of cancers.

Understanding proteins and pathways involved in disease does not automatically lead to new therapies.

An example is the development of inhibitors of matrix metalloproteinases (MMPs), a family of enzymes that has been linked to metastasis, the major cause of death from cancer.

Early clinical trials of MMP inhibitors failed to show any survival benefit in cancer patients, but progress in this field continues to be made by researchers including Lynn Matrisian, Ph.D., chair of Cancer Biology at Vanderbilt-Ingram, who participated in last week's meeting.

Also at the meeting, Richard Caprioli, Ph.D., director of the Vanderbilt Mass Spectrometry Research Center, and Daniel Liebler, Ph.D., director of the Vanderbilt Proteomics Laboratory, described how technologies for identifying and analyzing proteins are speeding the exploration the matrix — and all of its acronyms.