Parathyroid hormone-related protein is an independent prognostic factor for renal cell carcinoma

Wu, Weicheng; Muramoto, Masatoshi; Ohori, Makoto; Egawa, Shin; Uchida, Τοyoaki; Baba, Shirō

doi:10.1002/(sici)1097-0142(19990915)86:6<1028::aid-cncr19>3.0.co;2-g

Cited by 34 publications

(27 citation statements)

References 31 publications

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“…Taken together with the results obtained with the PTH1R antagonist, these results suggest that the CCRC-derived PTHrP species, which acts as a survival factor, may contain both NH 2 -and COOH-terminal determinants, and that this species may be the major CCRC-derived PTHrP fragment. Interestingly, investigating COOHterminal PTHrP (109 -141) expression in human CCRC by immunohistochemistry using a specific antibody, Iwamura et al (13) have shown that the expression of the COOH-terminal PTHrP (109 -141) in CCRC may be associated with lower CCRC recurrence after radical nephrectomy. They hypothesized that the COOH-terminal PTHrP fragment might have an inhibitory effect on CCRC cell growth.…”

Section: Discussionmentioning

confidence: 66%

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Parathyroid Hormone-Related Protein Is an Essential Growth Factor for Human Clear Cell Renal Carcinoma and a Target for the von Hippel-Lindau Tumor Suppressor Gene

et al. 2004

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Section: Discussionmentioning

confidence: 66%

“…Moreover, PTHrP is expressed in 95% of CCRC in humans, whether they are associated with hypercalcemia or not (12,13). In 1990, Burton et al (14) showed that PTHrP regulates the proliferation of a human PTHrP-secreting CCRC cell line (SKRC-1) in vitro.…”

Section: Introductionmentioning

confidence: 99%

Parathyroid Hormone-Related Protein Is an Essential Growth Factor for Human Clear Cell Renal Carcinoma and a Target for the von Hippel-Lindau Tumor Suppressor Gene

et al. 2004

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“…Associations between PTHrP and prolongation of survival have also been observed in studies of pancreatic cancer and breast cancer. Renal carcinoma patients with strong tumor PTHrP staining using the same COOH-terminal PTHrP antibody we used had 87% of 5-year disease-free survival compared with 50% for patients with minimal staining (30). In breast carcinomas, PTHrP 1-14 immunoreactivity was associated with a smaller yet statistically significant increase in 5-year survival rate, 87% (95% confidence interval, 82-91%; n = 265) compared with 73% (63-81%; n = 102) for patients with PTHrP-positive and PTHrP-negative tumors, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Peptides in the COOH-terminal PTHrP domain are active against osteoclasts (34) but direct effects on cancer cells have not been described. The studies in which PTHrP had a positive prognostic role in cancer used an antibody to PTHrP 1-14 for breast cancer, one directed against PTHrP 126-136 in renal cell carcinoma and our study (1,18,30). Furthermore, the small cell lung cancer case report and the NSCLC case series in which PTHrP apparently associated with more aggressive malignancies used NH 2 -terminal and COOH-terminal PTHrP antibodies, respectively (31,32).…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Survival Advantage with Parathyroid Hormone–Related Protein in Non–Small Cell Lung Carcinoma Patients

Hastings¹,

Laux²,

Casillas³

et al. 2006

Clinical Cancer Research

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Purpose: Parathyroid hormone^related protein (PTHrP) is commonly expressed in non^small cell lung carcinomas (NSCLC). Expression of the protein could have implications for progression of the disease because it regulates cancer cell growth, apoptosis, and angiogenesis. However, its relationship with survival has not been evaluated in a large-scale investigation. Experimental Design: PTHrP expression was assessed in paraffin-embedded tumor samples from 407 patients with NSCLC by immunohistochemistry. A pathologist unaware of the clinical history classified specimens as PTHrP positive or PTHrP negative. The log-rank test was used to compare survivals of PTHrP-positive and PTHrP-negative groups, and Cox regression was used to adjust for additional covariates.Results: Median survival was 55 versus 22 months (P < 0.001) in female patients with and without tumor PTHrP, respectively. Male survival was 38 months independent of PTHrP status. Stage, histology, age, and smoking history were also associated with increased longevity. PTHrP remained a significant predictor of survival for female patients after controlling for stage, histology, and age. Conclusions: In this study, PTHrP expression was associated with a survival advantage in female patients. Additional investigations must be done to ascertain whether the result is reproducible and independent of potential confounding covariates. Sex-dependent effects of PTHrP in lung cancer would open new avenues of research into the role of sex in cancer progression.Parathyroid hormone-related protein (PTHrP) was discovered as the factor responsible for hypercalcemia of malignancy. As the name implies, PTHrP shares structural similarities with PTH, specifically in the NH 2 -terminal 34 amino acids. Consequently, PTHrP 1-34 binds to the same receptor as PTH 1-34, the type 1 PTH/PTHrP receptor (PTH1R), and duplicates the effects of PTH 1-34 in tissues that bear the receptor, including causing hypercalcemia. Hypercalcemic effects are mediated through decreases in calcium excretion in kidney and increases in calcium release from bone. It is less widely appreciated that PTHrP also exerts effects direct effects on cancer cells that could be important in the pathology of malignancy.

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“…In human cancer, the possible association between PTHLH polymorphisms, expression of speci®c PTHrP peptides and tumor prognosis awaits extensive analysis. However, a role for PTHrP peptide (109 ± 141) expression as an independent prognostic factor for renal cell carcinoma has been suggested (Iwamura et al, 1999). We reported an association between cancer survival in lung adenocarcinoma patients and PTHLH polymorphism at a variable number of tandem repeats region located 100 bp downstream of exon 5, i.e., close to the osteostatin-encoding exon 4 (Mangin et al, 1990;Manenti et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

A cancer modifier role for parathyroid hormone-related protein

et al. 2000

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Parathyroid hormone-related protein is an independent prognostic factor for renal cell carcinoma

Cited by 34 publications

References 31 publications

Parathyroid Hormone-Related Protein Is an Essential Growth Factor for Human Clear Cell Renal Carcinoma and a Target for the von Hippel-Lindau Tumor Suppressor Gene

Parathyroid Hormone-Related Protein Is an Essential Growth Factor for Human Clear Cell Renal Carcinoma and a Target for the von Hippel-Lindau Tumor Suppressor Gene

Sex-Specific Survival Advantage with Parathyroid Hormone–Related Protein in Non–Small Cell Lung Carcinoma Patients

A cancer modifier role for parathyroid hormone-related protein

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