Bone is the most common site of metastases for solid tumors such as
breast, prostate and bladder cancers. These metastases contribute
significantly to the morbidity and mortality of these cancers.
Significant progress has been made in the understanding of the molecular
mechanisms underlying osteolytic bone metastases particularly from
breast cancer. However, in advanced prostate cancer and to some degree
bladder cancer, patients tend to present with osteoblastic lesions or
mixed osteolytic-osteoblastic bone metastases.
Much less is known about
the mechanisms leading to these types of bone metastases. Our initial
studies have lead to the development of reliable animal models of
prostate cancer metastases to bone and bladder cancer metastases to
bone. We have also shown that androgen deprivation, a common treatment
for advanced prostate cancer, can increase the incidence of bone
Dr. Susan Padalecki's lab focus is to utilize these models of bone metastasis
to dissect the pathophysiology of prostate cancer and bladder cancer
metastases to bone as well as for use in pre-clinical testing of
therapeutics. Identification of specific molecular targets for the
development of therapeutics is a key goal in this work.
Hilton WM, Padalecki SS, Ankerst DP, Leach RJ, Thompson IM. Temporal changes in the clinical approach to diagnosing prostate cancer. J Natl Cancer Inst Monogr. 2012 Dec;2012(45):162-8.
Johnson RW, Nguyen MP, Padalecki SS, Grubbs BG, Merkel AR, Oyajobi BO, Matrisian LM, Mundy GR, Sterling JA. TGF-beta promotion of Gli2-induced expression of parathyroid hormone-related protein, an important osteolytic factor in bone metastasis, is independent of canonical Hedgehog signaling. Cancer Res. 2011 Feb 1;71(3):822-31.
Hall DC, Johnson-Pais TL, Grubbs B, Bernal R, Leach RJ, Padalecki SS. Maspin reduces prostate cancer metastasis to bone. Urol Oncol. 2008 Nov-Dec;26(6):652-8.
Zhang Y, Padalecki SS, Chaudhuri AR, De Waal E, Goins BA, Grubbs B, Ikeno Y, Richardson A, Mundy GR, Herman B. Caspase-2 deficiency enhances aging-related traits in mice. Mech Ageing Dev. 2007 Feb;128(2):213-21.
Sterling JA, Oyajobi BO, Grubbs B, Padalecki SS, Munoz SA, Gupta A, Story B, Zhao M, Mundy GR. The
hedgehog signaling molecule Gli2 induces parathyroid hormone-related
peptide expression and osteolysis in metastatic human breast cancer
cells. Cancer Res. 2006 Aug 1;66(15):7548-53.