Lung carcinoma progression and survival versus amino- and carboxyl-parathyroid hormone-related protein expression.

Autor: Hastings RH; Anesthesiology Service, VA Medical Center (125), VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA, 92161, USA. rhhastings@ucsd.edu.; Research Service, VA San Diego Healthcare System, San Diego, USA. rhhastings@ucsd.edu.; Department of Anesthesiology, UC San Diego, San Diego, USA. rhhastings@ucsd.edu., Montgrain PR; Research Service, VA San Diego Healthcare System, San Diego, USA.; Medicine Service, VA San Diego Healthcare System, San Diego, USA.; Department of Medicine, UC San Diego, San Diego, USA., Quintana RA; Research Service, VA San Diego Healthcare System, San Diego, USA., Chobrutskiy B; Research Service, VA San Diego Healthcare System, San Diego, USA., Davani A; Research Service, VA San Diego Healthcare System, San Diego, USA., Miyanohara A; Viral Vector Core, UC San Diego, San Diego, USA., Mahooti S; Pathology Service, VA San Diego Healthcare System, San Diego, USA.
Jazyk: angličtina
Zdroj: Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2017 Aug; Vol. 143 (8), pp. 1395-1407. Date of Electronic Publication: 2017 Mar 25.
DOI: 10.1007/s00432-017-2396-4
Abstrakt: Purpose: Expression of the carboxyl PTHrP region of parathyroid hormone-related protein (PTHrP) is a positive prognostic indicator in women with lung cancer, but amino PTHrP is a negative indicator in other lung cancer patients. This project investigated whether PTHrP could be expressed as predominantly amino PTHrP or carboxyl PTHrP in individual lung carcinomas. It also assessed domain-specific effects on cancer progression and patient survival.
Methods: PTHrP immunoreactivities were analyzed versus survival in a human lung cancer tissue microarray (TMA). Growth was compared in athymic mice for isogenic lung carcinoma xenografts differing in expression of amino and carboxyl PTHrP domains.
Results: In the TMA, 33 of 99 patient tumors expressed only one PTHrP domain, while 54 expressed both. By Cox regression, the hazard ratio for cancer-specific mortality (95% confidence interval) was 2.6 (1.28-5.44) for amino PTHrP (P = 0.008) and 0.6 (0-2.58) for carboxyl PTHrP (P = 0.092). Xenografts of H358 lung adenocarcinoma cells that overexpressed amino PTHrP grew twice as fast as isogenic low PTHrP tumors in athymic mice, but growth of tumors expressing amino plus carboxyl PTHrP was not significantly different than growth of the control tumors. In summary, the presence of amino PTHrP signifies worse prognosis in lung cancer patients. In mouse xenografts, this effect was abrogated if carboxyl PTHrP was also present.
Conclusion: Amino PTHrP and carboxyl PTHrP can vary independently in different lung carcinomas. Carboxyl PTHrP may temper the stimulatory effect of amino PTHrP on cancer progression.
Databáze: MEDLINE
Externí odkaz: