Parathyroid hormone-related protein serves as a prognostic indicator in oral squamous cell carcinoma

Lv, Zhongjing; Wu, Xiangbing; Cao, Wei; Shen, Zongze; Wang, Lizhen; Xie, Fuqiang; Zhang, Jianjun; Ji, Tong; Yan, Ming; Chen, Wantao

doi:10.1186/s13046-014-0100-y

Cited by 27 publications

(23 citation statements)

References 53 publications

(59 reference statements)

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“…Both RUNX2 and PTHLH may play certain roles in tumor cell transformation, growth, metastasis, hypercalcemia, and cachexia2829. PTHLH has been reported as a poor prognosis marker of HNSCC1230, however, the role of PTHLH in HNSCC progression is unclear. In this study, we investigated the role of PTHLH in head and neck cancer by analyzing its expression in clinical patients and its phenotypic impact by investigating in vitro and in vivo cell growth due to PTHLH in HNSCC.…”

Section: Discussionmentioning

confidence: 99%

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Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation

Chang

Lin

et al. 2017

Sci Rep

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Parathyroid Hormone-Like Hormone (PTHLH) is an autocrine/paracrine ligand that is up-regulated in head and neck squamous cell carcinoma (HNSCC). However, the cellular function and regulatory mechanism in HNSCC remains obscure. We investigated the clinical significance of PTHLH in HNSCC patients, and verified the role of RUNX2/PTHLH axis, which is stimulated HNSCC cell growth. In patients, PTHLH is a poor prognosis marker. PTHLH expression lead to increasing the cell proliferation potential through an autocrine/paracrine role and elevating blood calcium level in Nod-SCID mice. In public HNSCC microarray cohorts, PTHLH is found to be co-expressed with RUNX2. Physiologically, PTHLH is regulated by RUNX2 and also acting as key calcium regulator. However, elevations of calcium concentration also increased the RUNX2 expression. PTHLH, calcium, and RUNX2 form a positive feedback loop in HNSCC. Furthermore, ectopic RUNX2 expression also increased PTHLH expression and promoted proliferation potential through PTHLH expression. Using cDNA microarray analysis, we found PTHLH also stimulated expression of cell cycle regulators, namely CCNA2, CCNE2, and CDC25A in HNSCC cells, and these genes are also up-regulated in HNSCC patients. In summary, our results reveal that PTHLH expression is a poor prognosis marker in HNSCC patients, and RUNX2-PTHLH axis contributes to HNSCC tumor growth.

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Section: Discussionmentioning

confidence: 99%

“…PTHLH promotes cell proliferation, migration, and invasion, and prevents apoptosis in different types of cancers91011. In HNSCC, PTHLH has been reported as a poor prognostic marker and is stimulated in vitro cell growth through promoting cell cycle progression12. However, the regulation mechanism and tumor progression role of PTHLH in HNSCC remains uncertain.…”

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confidence: 99%

Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation

Chang

Lin

et al. 2017

Sci Rep

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“…In the present study, we found that ICC cells produced PTHLH ligands that respond via the expression of cognate receptors PTH1R, resulting in the continuous activation of downstream signaling pathways. Extensive evidence suggest that PTHLH is viewed as a cellular cytokine, particularly in epithelial cancer cells, that exhibits an autocrine or paracrine role in both cell growth and differentiation [ 26 , 27 ]. In our previous study, we found that overexpression of the PTHLH (LV-PTHLH), which transfects lentivirus-mediated PTHLH GFP without deleting endogenous PTHLH expression in ICC cells, may enter into the non-proliferative cells (data not show).…”

Section: Discussionmentioning

confidence: 99%

Autocrine parathyroid hormone-like hormone promotes intrahepatic cholangiocarcinoma cell proliferation via increased ERK/JNK-ATF2-cyclinD1 signaling

Tang

Liao

et al. 2017

J Transl Med

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Background and aimsIntrahepatic cholangiocarcinoma (ICC) is an aggressive tumor with a high fatality rate. It was recently found that parathyroid hormone-like hormone (PTHLH) was frequently overexpressed in ICC compared with non-tumor tissue. This study aimed to elucidate the underlying mechanisms of PTHLH in ICC development.MethodsThe CCK-8 assay, colony formation assays, flow cytometry and a xenograft model were used to examine the role of PTHLH in ICC cells proliferation. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins. Luciferase reporter, chromatin immunoprecipitation (ChIP) and DNA pull-down assays were used to verify the transcription regulation of activating transcription factor-2 (ATF2).ResultsPTHLH was significantly upregulated in ICC compared with adjacent and normal tissues. Upregulation of PTHLH indicated a poor pathological differentiation and intrahepatic metastasis. Functional study demonstrated that PTHLH silencing markedly suppressed ICC cells growth, while specific overexpression of PTHLH has the opposite effect. Mechanistically, secreted PTHLH could promote ICC cell growth by activating extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and subsequently upregulated ATF2 and cyclinD1 expression. Further study found that the promoter activity of PTHLH were negatively regulated by ATF2, indicating that a negative feedback loop exists.ConclusionsOur findings demonstrated that the ICC-secreted PTHLH plays a characteristic growth-promoting role through activating the canonical ERK/JNK-ATF2-cyclinD1 signaling pathways in ICC development. We identified a negative feedback loop formed by ATF2 and PTHLH. In this study, we explored the therapeutic implication for ICC patients.Electronic supplementary materialThe online version of this article (10.1186/s12967-017-1342-1) contains supplementary material, which is available to authorized users.

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“…The relationship of IL‐11 to tumor progression and metastasis has been described in other cancers, such as bladder cancer and renal carcinoma . Likewise, PTHrP expressed in OSCCs and other malignant tumors seems to stimulate the activity of osteoclasts, acting both in osteoclastic and osteoblastic cells; moreover, it is related to increased tumor cell proliferation, survival, adhesion, migration and invasion, and is considered an indicator of the prognosis . Related to this, the present study showed that SCC9 cells expressed the IL‐11 and PTHrP genes, which is in agreement with previous reports .…”

Section: Discussionmentioning

confidence: 99%

Photomodulation of the osteoclastogenic potential of oral squamous carcinoma cells

Schalch

Fernandes

Costa‐Rodrigues

et al. 2016

Journal of Biophotonics

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The treatment for oral cancer usually involves surgical excision followed by chemotherapy and/or radiotherapy. The combination of these therapies generally promotes a serious inflammation of the mucosa of the digestive tract, denominated mucositis, which compromises continuity of treatment. Photobiomodulation (PBM) therapy has been used successfully to reduce the oral mucositis, however there is still some controversy regarding the effects of this therapy on unintentionally irradiated tumor cells that may remain after cancer treatment. The aim of this study was to analyze the effect of PBM therapy (using parameters for mucositis) on the modulation of osteoclastogenic potential of a cell line derived from human lingual squamous cell carcinoma (SCC9). Previously irradiated SCC9 cells were co-cultured with human osteoclast precursors. Co-cultures performed with non-irradiated SCC9 cells served as control. After 7, 14 and 21 days the co-cultures were evaluated for the tartrate-resistant acid phosphatase (TRAP) activity, an osteoclastogenic marker. Additionally, the monocultures of SCC9 cells (non-irradiated and irradiated) were analyzed for cell viability/proliferation and for the expression of IL-11 and PTHrP. The irradiation of SCC9 cells with PBM with an energy density of 4 J/cm decreased the pro-osteoclastogenic potential of those cells. This may represent a potential useful side effect of PBM therapy. PBM (using recommended parameters for mucositis treatment) decreases the osteoclastogenic potential of oral squamous carcinoma cells.

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Parathyroid hormone-related protein serves as a prognostic indicator in oral squamous cell carcinoma

Cited by 27 publications

References 53 publications

Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation

Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation

Autocrine parathyroid hormone-like hormone promotes intrahepatic cholangiocarcinoma cell proliferation via increased ERK/JNK-ATF2-cyclinD1 signaling

Photomodulation of the osteoclastogenic potential of oral squamous carcinoma cells

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