Effective targeting of the tumor microenvironment for cancer therapy.

Background: The tumor microenvironment is an emerging source of novel therapeutic targets in cancer. The glycosaminoglycan hyaluronan (HA) accumulates in 20-30% of tumors and is often associated with poor prognosis.

Materials And Methods: We developed a digitized, semiquantitative scoring system for tumor-associated HA content, then grouped tumors (from animal models or patients) according to the degree of HA accumulation (HA+1,2,3).

PTHrP stimulates prostate cancer cell growth and upregulates aldo-keto reductase 1C3.

The aim of the study was to demonstrate the role of parathyroid hormone related protein (PTHrP) in stimulating aldo-keto reductase (AKR) 1C3 expression in prostate cancer (CaP) cells. CaP cell proliferation and resistance to apoptosis was increased by PTHrP transfection. Conversely, reducing AKR1C3 expression by siRNA decreased cell proliferation.

Parathyroid hormone-related protein regulates apoptosis in lung cancer cells through protein kinase A.

Parathyroid hormone-related protein (PTHrP)-(1-34) and PTHrP-(140-173) protect lung cancer cells from apoptosis after ultraviolet (UV) irradiation. This study evaluated upstream signaling in PTHrP-mediated alteration of lung cancer cell sensitivity to apoptosis. The two peptides increased cAMP levels in BEN lung cancer cells by 15-35% in a dose-dependent fashion, suggesting signaling through protein kinase A (PKA).

Parathyroid hormone-related protein ameliorates death receptor-mediated apoptosis in lung cancer cells.

Parathyroid hormone-related protein (PTHrP) is expressed in more advanced, aggressive tumors and may play an active role in cancer progression. This study investigated the effects of PTHrP on apoptosis after UV irradiation, Fas ligation, or staurosporine treatment in BEN human squamous lung carcinoma cells. Cells at 70% confluency were treated for 24 h with 100 nM PTHrP-(1-34), PTHrP-(38-64), PTHrP-(67-86), PTHrP-(107-139), or PTHrP-(140-173) in media with serum, exposed for 30 min to UV-B radiation (0.