Molecular mechanisms in bone metastases of breast and prostate cancer, translation models to test efficacy of pharmaceutical interventions

The principal interests of the Guise laboratory encompass skeletal complications of malignancy: tumor metastasis to bone and the effect of cancer treatment on skeletal health.  Specifically, the molecular mechanisms by which tumor cells interact with bone cells to cause either bone destruction (osteolytic metastases) or new bone formation (osteoblastic metastases) are investigated starting at the molecular level to whole animal mouse models of bone metastases.  The effect of cancer treatments, such as androgen deprivation for prostate cancer and aromatase inhibitors for breast cancer, on bone mass as well as the development and progression of bone metastasis is under investigation in animal models as well as clinical trials.

Active projects in the laboratory include: 1) the role of TGFb and PTHrP in breast cancer bone metastases; 2) Adrenomedullin in prostate cancer bone metastases; 3) CCN proteins in breast cancer bone metastases; 4) role of hypoxia inducible factor a in regulating tumor-produced osteoblast and osteoclast-stimulating factors in breast and prostate cancer metastases to bone; 5) role of TGFb in prostate cancer metastases to bone and the effect of serine-threonine kinase receptor blockade; 6) role of endothelin axis in normal and pathological bone remodeling; 7) TGFb regulation of CCN proteins; 8) role of high bone turnover state induced by estrogen deficiency on the development and progression of breast cancer metastases to bone; 9) the effect of aromatase inhibition on estrogen target organs of breast, bone and GH-IGF-1 axis.

The Guise laboratory has active collaborations with the Chirgwin laboratory on CCN proteins, adrenomedullin and TGFb in bone metastases; with the Theodorescu laboratory on the endothelin axis in bladder cancer metastases to lung; with the S. Parson's laboratory on adrenomedullin in prostate cancer and CCN proteins in breast cancer bone metastases; and with Weber laboratory on MAPK inhibition in prostate cancer bone metastases.  The Guise laboratory utilizes the small animal imaging core as well as the biomolecular facility core to perform xenogen imaging of tumor metastases in mice and microarray gene analysis respectively