[MLN-464(?) for cancer]
This first showed up in PNAS today despite the Washington U. PR -- which came out a week ago -- pointed to by Wilder. Said PR explains the significance:
Message 19466613
It was not noted that a MLNM drug was the used here; I'm making that assumption based on the info. It is not identified by that name in the pipeline.
>>Published online before print November 11, 2003
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.2234372100
Medical Sciences
Platelet and osteoclast 3 integrins are critical for bone metastasis
Suzanne J. Bakewell *, Patrick Nestor , Srinivasa Prasad , Michael H. Tomasson , Nikki Dowland , Mukund Mehrotra , Robert Scarborough , James Kanter , Keith Abe , David Phillips , and Katherine N. Weilbaecher
*Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 505, Little Rock, AR 72205; Departments of Medicine and Pathology, Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8069, St. Louis, MO 63110; and Department of Cardiovascular Biology, Millennium Pharmaceuticals, 256 East Grand Avenue, South San Francisco, CA 94080
Edited by Philip W. Majerus, Washington University School of Medicine, St. Louis, MO, and approved September 12, 2003 (received for review July 12, 2003)
Mice with a targeted deletion of 3 integrin were used to examine the process by which tumor cells metastasize and destroy bone. Injection of B16 melanoma cells into the left cardiac ventricle resulted in osteolytic bone metastasis in 74% of 3+/+ mice by 14 days. In contrast, only 4% of 3-/- mice developed bone lesions. Direct intratibial inoculation of tumor resulted in marrow replacement by tumor in 3-/- mice, but no associated trabecular bone resorption as seen in 3+/+ mice. Bone marrow transplantation studies showed that susceptibility to bone metastasis was conferred by a bone marrow-derived cell. To dissect the roles of osteoclast and platelet 3 integrins in this model of bone metastasis, osteoclast-defective src-/- mice were used. Src-null mice were protected from tumor-associated bone destruction but were not protected from tumor cell metastasis to bone. In contrast, a highly specific platelet aggregation inhibitor of activated IIb3 prevented B16 metastases. These data demonstrate a critical role for platelet IIb3 in tumor entry into bone and suggest a mechanism by which antiplatelet therapy may be beneficial in preventing the metastasis of solid tumors.<<
Cheers, Tuck |
