This ongoing Program Project Grant was originally initiated in 1985 in order to develop a team approach to clarifying the mechanisms by which common malignancies such as breast cancer and myeloma affect the skeleton and cause disastrous clinical consequences. This area of research has evolved since the original application. Since identification of the major tumor- associated factors in the 1980s, our emphasis has changed so that a major objective now is to understand how these factors interact to cause the characteristic osteolytic and osteoblastic lesions seen in different types of malignancy. Our key accomplishments in the last grant period have been to develop new in vivo models of osteolytic and osteoblastic lesions associated with solid tumors and myeloma bone disease; to show the importance of the bone microenvironment in tumor cell behavior in bone; to demonstrate the anti-tumor effects of bisphosphonates on solid tumors; and to demonstrate in vivo the key roles of TGFbeta and PTH-rP in local osteolysis in breast cancer. We have assembled a team of investigators with skills in bone cell biology, molecular biology, protein chemistry, and bone histomorphometry to use state-of-the-art techniques for examining the mechanisms by which bone cell function is altered in a number of in vivo models of human tumors. In the 12 years our team has had support from this grant, we have presented 150 abstracts and published over 400 manuscripts in the general area supported by this grant, and 138 manuscripts which can be directly ascribed to it since the last competitive renewal in 1994. During the next grant period, we emphasize three features of our experimental approaches. 1) reliance in each project on well-described animal models of bone disease which occur in different common human malignancies; 2) extensive use of the powerful morphologic technique of quantitative bone histomorphometry in these in vivo models; and 3) examination of the role of bone itself in promoting growth of those tumors which have a special predilection for bone sites such as breast cancer and myeloma. Our hope is that as we gain insights into mechanisms by which tumor cells affect bone cell function, we will develop novel approaches for preventing these effects or reversing them once they have become established. These animal models should enable us to gain information on this common complication of many cancers which is not possible to gather in patients with terminal malignancy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
3P01CA040035-16S2
Application #
6577055
Study Section
Subcommittee G - Education (NCI)
Program Officer
Rosenfeld, Bobby
Project Start
1985-09-30
Project End
2004-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
16
Fiscal Year
2002
Total Cost
$112,146
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Arnold Egloff, Shanna A; Du, Liping; Loomans, Holli A et al. (2017) Shed urinary ALCAM is an independent prognostic biomarker of three-year overall survival after cystectomy in patients with bladder cancer. Oncotarget 8:722-741
Arnold, Shanna A; Loomans, Holli A; Ketova, Tatiana et al. (2016) Urinary oncofetal ED-A fibronectin correlates with poor prognosis in patients with bladder cancer. Clin Exp Metastasis 33:29-44
Preston Campbell, J; Mulcrone, P; Masood, S K et al. (2015) TRIzol and Alu qPCR-based quantification of metastatic seeding within the skeleton. Sci Rep 5:12635
Sharma, Ramaswamy; Williams, Paul J; Gupta, Anjana et al. (2015) A dominant-negative F-box deleted mutant of E3 ubiquitin ligase, ?-TrCP1/FWD1, markedly reduces myeloma cell growth and survival in mice. Oncotarget 6:21589-602
Seeley, Erin H; Wilson, Kevin J; Yankeelov, Thomas E et al. (2014) Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease. Bone 61:208-16
Johnson, Rachelle W; Merkel, Alyssa R; Page, Jonathan M et al. (2014) Wnt signaling induces gene expression of factors associated with bone destruction in lung and breast cancer. Clin Exp Metastasis 31:945-59
Ding, Hao; Nyman, Jeffry S; Sterling, Julie A et al. (2014) Development of Raman spectral markers to assess metastatic bone in breast cancer. J Biomed Opt 19:111606
Hansen, Amanda G; Arnold, Shanna A; Jiang, Ming et al. (2014) ALCAM/CD166 is a TGF-?-responsive marker and functional regulator of prostate cancer metastasis to bone. Cancer Res 74:1404-15
Waning, David L; Mohammad, Khalid S; Guise, Theresa A (2013) Cancer-associated osteoclast differentiation takes a good look in the miR(NA)ror. Cancer Cell 24:407-9
Jin, Renjie; Sterling, Julie A; Edwards, James R et al. (2013) Activation of NF-kappa B signaling promotes growth of prostate cancer cells in bone. PLoS One 8:e60983

Showing the most recent 10 out of 210 publications