Parathyroid Hormone-Related Protein (PTHrP): An Emerging Target in Cancer Progression and Metastasis

2019 ◽  
pp. 161-178 ◽  
Author(s):  
Rui Zhang ◽  
Jiarong Li ◽  
Gloria Assaker ◽  
Anne Camirand ◽  
Siham Sabri ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cancer Progression ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein

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

2003 ◽  
Vol 285 (6) ◽  
pp. C1429-C1436 ◽  
Author(s):  
Randolph H. Hastings ◽  
Flavio Araiza ◽  
Douglas W. Burton ◽  
Lu Zhang ◽  
Maxwell Bedley ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Parathyroid Hormone ◽  
Cancer Cells ◽  
Uv Irradiation ◽  
Cancer Progression ◽  
Caspase 3 ◽  
Death Receptor ◽  
Related Protein ◽  
Caspase 9 ◽  
Parathyroid Hormone Related Protein

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 (0.9 mJ/cm2), and maintained for another 24 h. Caspase-3, caspase-8, and caspase-9 activities increased fivefold. Pretreatment with PTHrP-(1-34) and PTHrP-(140-173) ameliorated apoptosis after UV irradiation, as indicated by reduced caspase activities, increased cell protein, decreased nuclear condensation, and increased clonal survival. Other peptides had no effect on measures of apoptosis. PTHrP-(140-173) also reduced caspase activities after Fas ligation by activating antibody, but neither peptide had effects on caspase-3 or caspase-9 activity after 1 μM staurosporine. These data indicate that PTHrP-(1-34) and PTHrP-(140-173) protect against death receptor-induced apoptosis in BEN lung cancer cells but are ineffective against mitochondrial pathways. PTHrP contributes to lung cancer cell survival in culture and could promote cancer progression in vivo. The mechanism for the protective effect against apoptosis remains to be determined.

Parathyroid Hormone–Related Protein Inhibits Endothelin-1 Production

Hypertension ◽  
1996 ◽  
Vol 27 (3) ◽  
pp. 360-363 ◽  
Author(s):  
Bingbing Jiang ◽  
Shigeto Morimoto ◽  
Keisuke Fukuo ◽  
Atsushi Hirotani ◽  
Michio Tamatani ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Related Protein ◽  
Endothelin 1 ◽  
Parathyroid Hormone Related Protein

Parathyroid Hormone–Related Protein Upregulates Interleukin-1β–Induced Nitric Oxide Synthesis

Hypertension ◽  
1997 ◽  
Vol 30 (4) ◽  
pp. 922-927 ◽  
Author(s):  
Bingbing Jiang ◽  
Shigeto Morimoto ◽  
Jin Yang ◽  
Keisuke Fukuo ◽  
Atsushi Hirotani ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Parathyroid Hormone ◽  
Interleukin 1Β ◽  
Nitric Oxide Synthesis ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein

scholarly journals Purification and Characterization of Recombinant Human Parathyroid Hormone-related Protein

1989 ◽  
Vol 264 (25) ◽  
pp. 14806-14811
Author(s):  
R G Hammonds ◽  
P McKay ◽  
G A Winslow ◽  
H Diefenbach-Jagger ◽  
V Grill ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Related Protein ◽  
Human Parathyroid Hormone ◽  
Purification And Characterization ◽  
Parathyroid Hormone Related Protein

scholarly journals Extracellular vesicles-released parathyroid hormone-related protein from Lewis lung carcinoma induces lipolysis and adipose tissue browning in cancer cachexia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenjun Hu ◽  
Hairong Xiong ◽  
Zeyuan Ru ◽  
Yan Zhao ◽  
Yali Zhou ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Parathyroid Hormone ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Cancer Cachexia ◽  
Lewis Lung ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Tissue Browning

AbstractCancer cachexia is a metabolic disorder characterized by skeletal muscle wasting and white adipose tissue browning. Specific functions of several hormones, growth factors, and cytokines derived from tumors can trigger cachexia. Moreover, adipose tissue lipolysis might explain weight loss that occurs owing to cachexia. Extracellular vesicles (EVs) are involved in intercellular communication. However, whether EVs participate in lipolysis induced by cancer cachexia has not been thoroughly investigated. Using Lewis lung carcinoma (LLC) cell culture, we tested whether LLC cell-derived EVs can induce lipolysis in 3T3-L1 adipocytes. EVs derived from LLC cells were isolated and characterized biochemically and biophysically. Western blotting and glycerol assay were used to study lipolysis. LLC cell-derived EVs induced lipolysis in vivo and vitro. EVs fused directly with target 3T3-L1 adipocytes and transferred parathyroid hormone-related protein (PTHrP), activating the PKA signaling pathway in 3T3-L1 adipocytes. Blocking PTHrP activity in LLC-EVs using a neutralizing antibody and by knocking down PTHR expression prevented lipolysis in adipocytes. Inhibiting the PKA signaling pathway also prevents the lipolytic effects of EVs. In vivo, suppression of LLC-EVs release by knocking down Rab27A alleviated white adipose tissue browning and lipolysis. Our data showed that LLC cell-derived EVs induced adipocyte lipolysis via the extracellular PTHrP-mediated PKA pathway. Our data demonstrate that LLC-EVs induce lipolysis in vitro and vivo by delivering PTHrP, which interacts with PTHR. The lipolytic effect of LLC-EVs was abrogated by PTHR knockdown and treatment with a neutralizing anti-PTHrP antibody. Together, these data show that LLC-EV-induced lipolysis is mediated by extracellular PTHrP. These findings suggest a novel mechanism of lipid droplet loss and identify a potential therapeutic strategy for cancer cachexia.

scholarly journals Parathyroid Hormone-Related Protein Induces Cachectic Syndromes without Directly Modulating the Expression of Hypothalamic Feeding-Regulating Peptides

2007 ◽  
Vol 13 (1) ◽  
pp. 292-298 ◽  
Author(s):  
Hirofumi Hashimoto ◽  
Yumiko Azuma ◽  
Makoto Kawasaki ◽  
Hiroaki Fujihara ◽  
Etsuro Onuma ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein
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