<scp>PDGFRA mRNA</scp> overexpression is associated with regional metastasis and reduced survival in oral squamous cell carcinoma

Ong, Hui Shan; Gokavarapu, Sandhya; Tian, Zhen; Jiang, Li; Xu, Qin; Zhang, Chen Ping; Cao, Wei

doi:10.1111/jop.12713

Cited by 17 publications

(11 citation statements)

References 22 publications

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“…Studies are beginning to emerge suggesting bone marrow derived mesenchymal cells may be an important source of circulating stromal cells in TME (3,9,41) and autocrine activation of PDGFR-α has been shown to promote epithelial ovarian cancer cell proliferation and thought to play a role in metaplastic transformation of mullerian epithelium (35). Our observations are further supported by Ong et al who recently reported overexpression of PDGFR-α mRNA was associated with advanced disease in patients with oral cavity squamous cell carcinoma (43,44).…”

Section: Discussionsupporting

confidence: 84%

Activation PDGFR-α/AKT Mediated Signaling Pathways in Oral Squamous Cell Carcinoma by Mesenchymal Stem/Stromal Cells Promotes Anti-apoptosis and Decreased Sensitivity to Cisplatin

et al. 2020

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Desmoplasia, a hallmark of a head and neck cancer, has both biologic and physiologic effects on cancer progression and chemotherapeutic response. Mesenchymal stem/stromal cells (MSCs), also known as mesenchymal stromal progenitor cells, have been shown to play a role in cancer progression, alter apoptotic responses, and confer resistance to chemotherapy in various carcinomas. The pathophysiology of MSCs with respect to tumorigenesis is widely reported in other cancers and is sparsely reported in oral squamous cell carcinomas (OSCCs). We previously reported paracrine mediated PDGF-AA/PDGFR-α signaling to underlie MSCs chemotaxis in OSCC. Given the poor clinical response to primary chemotherapy, we hypothesized that MSCs may alter cancer cell sensitivity to cisplatin through activation of PDGFR-α mediated signaling pathways. Co-culture of MSCs with human derived OSCC cell lines, JHU-012 and −019, resulted in a significant increase in the production of PDGF-AA and MCP-1 compared to cancer cells grown alone (p < 0.005) and was accompanied by an increase in the phosphorylation state of PDGFR-α (p < 0.02) and downstream target AKT at S473 (p < 0.025) and T308 (p < 0.02). JHU-012 and −019 cancer cells grown in co-culture were significantly less apoptotic (p < 0.001), expressed significantly higher levels of Bcl-2 (p < 0.04) with a concomitant significant decrease in bid expression (p < 0.001) compared to cancer cells grown alone. There was a significant increase in the cisplatin dose response curve in cancer cell clones derived from JHU-012 and 019 cancer cells grown in co-culture with MSCs compared to clones derived from cancer cells grown alone (p < 0.001). Moreover clones derived from JHU-012 cells grown in co-culture with MSCs were significantly more susceptible to cisplatin following pretreatment with, crenolanib, a PDGFR inhibitor, Wang et al. PDGFR-α/AKT Signaling in Oral Cancer compared to cancer cells grown alone or in co-culture with MSCs (p < 0.0001). These findings suggest that crosstalk between cancer cells and MSCs is mediated, at least in part, by activation of autocrine PDGF-AA/PDGFR-α loop driving AKT-mediated signaling pathways, resulting in reduced cancer cell sensitivity to cisplatin through alterations in apoptosis.

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Section: Discussionsupporting

confidence: 84%

Activation PDGFR-α/AKT Mediated Signaling Pathways in Oral Squamous Cell Carcinoma by Mesenchymal Stem/Stromal Cells Promotes Anti-apoptosis and Decreased Sensitivity to Cisplatin

et al. 2020

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“…Chemoattractants such as CXCL1 may help in recruiting non-malignant supportive cells such as neutrophils, which have ample functions as tumor-associated neutrophils (TANs) in the tumor environment [ 125 ]. Furthermore, platelet-derived growth factor receptors alpha and beta (PDGFR-A/B) have been associated with an induction of resistance to cisplatin, anti-apoptotic traits, and metastases formation [ 126 , 127 ]. Four out of eight gene sets enriched in low-risk patients were associated with mRNA metabolism and cell cycle regulation [ 123 ], which could potentially explain a better response to R(C)T in cycling cells and subsequent reduction of recurrences.…”

Section: Emt In Hnsccmentioning

confidence: 99%

Epithelial-to-Mesenchymal Transition-Derived Heterogeneity in Head and Neck Squamous Cell Carcinomas

Baumeister

Zhou

Canis

et al. 2021

Cancers

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Head and neck squamous cell carcinomas (HNSCC) are common tumors with a poor overall prognosis. Poor survival is resulting from limited response to multi-modal therapy, high incidence of metastasis, and local recurrence. Treatment includes surgery, radio(chemo)therapy, and targeted therapy specific for EGFR and immune checkpoint inhibition. The understanding of the molecular basis for the poor outcome of HNSCC was improved using multi-OMICs approaches, which revealed a strong degree of inter- and intratumor heterogeneity (ITH) at the level of DNA mutations, transcriptome, and (phospho)proteome. Single-cell RNA-sequencing (scRNA-seq) identified RNA-expression signatures related to cell cycle, cell stress, hypoxia, epithelial differentiation, and a partial epithelial-to-mesenchymal transition (pEMT). The latter signature was correlated to nodal involvement and adverse clinical features. Mechanistically, shifts towards a mesenchymal phenotype equips tumor cells with migratory and invasive capacities and with an enhanced resistance to standard therapy. Hence, gradual variations of EMT as observed in HNSCC represent a potent driver of tumor progression that could open new paths to improve the stratification of patients and to innovate approaches to break therapy resistance. These aspects of molecular heterogeneity will be discussed in the present review.

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“…To the best of our knowledge, the process of cell proliferation, invasion and migration is essential for cancer metastasis. Therefore, interdiction of this progress is an efficient strategy to resist OSCC metastasis [22,23].…”

Section: Resultsmentioning

confidence: 99%

CXCL14 regulates cell proliferation, invasion, migration and epithelial-mesenchymal transition of oral squamous cell carcinoma

Liang

Wang

et al. 2019

Biotechnology & Biotechnological Equipment

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PDGFRA mRNA overexpression is associated with regional metastasis and reduced survival in oral squamous cell carcinoma

Abstract: PDGFRA overexpression in oral SCC, in respect to strong PDGFRA immunohistochemical staining and high PDGFRA mRNA expression, was positively associated with regional metastasis and reduced patient survival.

Cited by 17 publications

References 22 publications

Activation PDGFR-α/AKT Mediated Signaling Pathways in Oral Squamous Cell Carcinoma by Mesenchymal Stem/Stromal Cells Promotes Anti-apoptosis and Decreased Sensitivity to Cisplatin

Activation PDGFR-α/AKT Mediated Signaling Pathways in Oral Squamous Cell Carcinoma by Mesenchymal Stem/Stromal Cells Promotes Anti-apoptosis and Decreased Sensitivity to Cisplatin

Epithelial-to-Mesenchymal Transition-Derived Heterogeneity in Head and Neck Squamous Cell Carcinomas

CXCL14 regulates cell proliferation, invasion, migration and epithelial-mesenchymal transition of oral squamous cell carcinoma

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