A mysterious molecule some scientists thought might speed the development of bladder cancer actually suppresses tumor growth, new research at the University of Virginia School of Medicine shows.
The discovery offers new understanding of the development of cancers in the urinary bladder, ovaries and elsewhere, and the findings point to potential new cancer therapies that would restore the protein where it’s missing.
The protein, known as SPARC (secreted protein acidic and rich in cysteine), acts as a tumor growth regulator in many cancers. In bladder cancer, the question was whether SPARC was promoting tumor growth or slowing it.
The new study determined that SPARC not only slowed the development and spread of bladder cancer, but also stopped the ability of tumors to make new blood vessels and prevented invasive and migrating cancer cells from attaching to prospective sites of distant metastasis.
Importantly, the study revealed that in less aggressive bladder tumors, SPARC is made by both cancer cells and the surrounding non-cancerous tissue and is associated with longer patient survival. In aggressive tumors, SPARC is diminished or lost in cancer cells while still made in the surrounding tissues and is associated with poor patient survival.
The distinct pattern of SPARC expression could explain previous observations of high SPARC in aggressive tumors that implied a possible tumor-promoting role of the protein.
The U.Va. study revealed that growing tumors lose SPARC while the surrounding healthy tissues respond by increasing SPARC production to restrain tumor progression. Using model systems, the research shows that growing tumors “inflame” surrounding healthy tissues, which reciprocate by increasing SPARC to stop the tumor. In essence, SPARC acts as an anti-inflammatory, attempting to heal inflammation instigated by tumors.
This correlation could prove extremely important, as the level and pattern of SPARC expression could offer doctors a way to gauge the progression and aggressiveness of the disease in patients.
“My aim is to identify whether SPARC can be restored in tumors that aren’t expressing it, and to identify how it synergizes with standard-of-care chemotherapy and radiation therapy, so we know when, exactly, to administer these particular treatment regimens,” said Dr. Neveen Said, lead author of the study. “That way we start with the right treatment for the right patient.”
She adds: “The new research is believed to be the first comprehensive study combining patient data with experimental models to address different angles of the bladder cancer initiation, progression and metastasis.”
The findings have been published in the February issue The Journal of Clinical Investigation online and in print. The article is authored by Said, of U.Va.’s Department of Radiation Oncology; Marta Sanchez-Carbayo of the Spanish National Cancer Institute in Madrid; Henry F. Frierson of U.Va.’s Department of Pathology; Marta Sanchez-Carbayo of the Spanish National Cancer Institute in Madrid, Spain; Rolf A. Brekken of the Department of Surgery at the University Texas Southwestern, in Dallas; and Dan Theodorescu, a former U.Va. researcher who now leads the University of Colorado Comprehensive Cancer Center.