By their 90th birthday, urologists say, 100 percent of allmen who live that long will have prostate trouble. Thatchestnut-sized gland will have swollen, either by benignhyperplasia or malignant carcinoma, to a bulk thatseriously impinges on urine flow.
Cancerous prostates will have long since metastasized,and killed more than 40,000 Americans during 1995alone. And six times as many new prostate cancer cases,244,000, will be diagnosed this year.
To be sure, prostate tumors are very slow-growing. Ascell biologist David Rowley observes, "A lot of men diefrom other causes before their prostate cancer kills them.So if one could simply slow down progression of thedisease, it would be a very effective way of treating it."
Rowley's research laboratory at Baylor College ofMedicine in Houston focuses on the cellular andhormonal factors that influence the embryonicdevelopment and geriatric demise of the prostate. He andhis co-workers have hit upon a 20-kiloDalton protein,hitherto unknown, that appears to inhibit the proliferationof prostate tissue, so far in rat cells at the test-tube level.
They report their discovery in the September Journal ofBiological Chemistry under the title: "Purification of anovel protein [ps20] from urogenital sinus mesenchymalcells with growth inhibitory properties in vitro."
What led Rowley and his colleagues to come upon thismolecule was educated curiosity. "We wanted to askquestions," he told BioWorld Today, "about some of thegrowth factors, differentiation factors or other proteinsinvolved in controlling the developing prostate gland inutero."
Their inquiry fixed on the fetal urogenital sinus, which,he explained, "is just a little pocket of tissue thatdevelops into the prostate gland. During that stage,rudimentary stromal cells make factors that affect thegrowth and differentiation of the rudimentary epithelialcells of the budding prostate gland.
"It's those very epithelial cells," Rowley continued, "thatlater in life become carcinomas. If we can fool thatcarcinoma into being embryonic again, maybe we canslow its growth."
That's where their new-found ps20 protein comes in. It isapparently responsible in utero for modulation _including inhibition _ of the growth and differentiationof those epithelial cells.
"We purified the protein with a variety of steps," Rowleyrecounted, "and at each step we assayed for its biologicalactivity, which inhibited the growth of human prostaticcarcinoma cells in vitro." Climaxing this experimentalprocess, the Baylor team determined the molecule'spartial amino-acid sequence, and found through data basesearch that "no known proteins share that sequence."
He and his co-workers are now pressing forward full bore"to clone the cDNA encoding this protein," Rowley said,"make a recombinant version, and test it for biologicalactivities, in culture and in animal tumors.
"Once we determine in the lab what its biologicalactivities are," he added, "the next step would be to goforward to actual clinical trials. But the project is still at avery early stage."
The recombinant route, he concluded, "is the only way, ifthis thing is ever to have any kind of commercialapplication."
Baylor's commercial partner, Sheffield MedicalTechnologies Inc., of Houston concurs. That company'svice-president for program development, biochemist AnnLevy, told BioWorld Today: "The diagnostic andtherapeutic potential for prostate cancer and possiblyother prostate growth-related diseases is very high. Weare excited about Dr. Rowley's work, which Sheffield isfunding."
Levy added, "Everything is now in his court. Progress hasbeen a little bit slower than we would have liked it to be,but when you're sequencing a gene, there are a lot ofunknowns that come in. We expect it to move at lightspeed, as soon as we have the recombinant protein.
"At that point," Levy observed, "we would step in andhave toxicology studies done at an outside lab. Then ofcourse, we would file an investigational new drugapplication, and take over from that point in time."
Sheffield has an option to license the technology inexclusivity, Levy said. "We are managing the intellectualproperty. All decisions are made jointly between Baylorand Sheffield, and we are funding the prosecution of thepatent applications and the patents." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.