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Neurotrophin Pathway Receptors NGFR and TrkA Control Perineural Invasion, Metastasis, and Pain in Oral Cancer.
Doan, Coleen; Aouizerat, Bradley E; Ye, Yi; Dang, Dongmin; Asam, Kesava; Bhattacharya, Aditi; Howard, Timothy; Patel, Yogin K; Viet, Dan T; Figueroa, Johnny D; Zhong, Jiang F; Thomas, Carissa M; Morlandt, Anthony B; Yu, Gary; Callahan, Nicholas F; Allen, Clint T; Grandhi, Anupama; Herford, Alan S; Walker, Paul C; Nguyen, Khanh; Kidd, Stephanie C; Lee, Steve C; Inman, Jared C; Slater, Jason M; Viet, Chi T.
Afiliação
  • Doan C; Department of Oral & Maxillofacial Surgery, Loma Linda University School of Dentistry, Loma Linda, CA, 92350, USA.
  • Aouizerat BE; Department of Oral & Maxillofacial Surgery, New York University College of Dentistry, New York, NY, 10010, USA.
  • Ye Y; Bluestone Center for Clinical Research, New York University College of Dentistry, New York, NY, 10010, USA.
  • Dang D; Department of Oral & Maxillofacial Surgery, New York University College of Dentistry, New York, NY, 10010, USA.
  • Asam K; Bluestone Center for Clinical Research, New York University College of Dentistry, New York, NY, 10010, USA.
  • Bhattacharya A; Department of Oral & Maxillofacial Surgery, New York University College of Dentistry, New York, NY, 10010, USA.
  • Howard T; Bluestone Center for Clinical Research, New York University College of Dentistry, New York, NY, 10010, USA.
  • Patel YK; Department of Oral & Maxillofacial Surgery, New York University College of Dentistry, New York, NY, 10010, USA.
  • Viet DT; Bluestone Center for Clinical Research, New York University College of Dentistry, New York, NY, 10010, USA.
  • Figueroa JD; Department of Oral & Maxillofacial Surgery, New York University College of Dentistry, New York, NY, 10010, USA.
  • Zhong JF; Bluestone Center for Clinical Research, New York University College of Dentistry, New York, NY, 10010, USA.
  • Thomas CM; Bluestone Center for Clinical Research, New York University College of Dentistry, New York, NY, 10010, USA.
  • Morlandt AB; Bluestone Center for Clinical Research, New York University College of Dentistry, New York, NY, 10010, USA.
  • Yu G; Bluestone Center for Clinical Research, New York University College of Dentistry, New York, NY, 10010, USA.
  • Callahan NF; Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, 92350, USA.
  • Allen CT; Department of Basic Sciences, Loma Linda University, School of Medicine, Loma Linda, CA, 92350, USA.
  • Grandhi A; Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
  • Herford AS; Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
  • Walker PC; Department of Oral and Maxillofacial Surgery, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
  • Nguyen K; Rory Meyers College of Nursing, New York University, New York, NY, 10003, USA.
  • Kidd SC; Department of Oral and Maxillofacial Surgery, University of Illinois Chicago, College of Dentistry, Chicago, IL, 60612, USA.
  • Lee SC; Section on Translational Tumor Immunology, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
  • Inman JC; Department of Oral & Maxillofacial Surgery, Loma Linda University School of Dentistry, Loma Linda, CA, 92350, USA.
  • Slater JM; Department of Oral & Maxillofacial Surgery, Loma Linda University School of Dentistry, Loma Linda, CA, 92350, USA.
  • Viet CT; Department of Otolaryngology, Loma Linda University School of Medicine, Loma Linda, CA, 92350, USA.
Adv Biol (Weinh) ; 6(9): e2200190, 2022 09.
Article em En | MEDLINE | ID: mdl-35925599
Oral squamous cell carcinoma (OSCC) patients suffer from poor survival due to metastasis or locoregional recurrence, processes that are both facilitated by perineural invasion (PNI). OSCC has higher rates of PNI than other cancer subtypes, with PNI present in 80% of tumors. Despite the impact of PNI on oral cancer prognosis and pain, little is known about the genes that drive PNI, which in turn drive pain, invasion, and metastasis. In this study, clinical data, preclinical, and in vitro models are leveraged to elucidate the role of neurotrophins in OSCC metastasis, PNI, and pain. The expression data in OSCC patients with metastasis, PNI, or pain demonstrate dysregulation of neurotrophin genes. TrkA and nerve growth factor receptor (NGFR) are focused, two receptors that are activated by NGF, a neurotrophin expressed at high levels in OSCC. It is demonstrated that targeted knockdown of these two receptors inhibits proliferation and invasion in an in vitro and preclinical model of OSCC, and metastasis, PNI, and pain. It is further determined that TrkA knockdown alone inhibits thermal hyperalgesia, whereas NGFR knockdown alone inhibits mechanical allodynia. Collectively the results highlight the ability of OSCC to co-opt different components of the neurotrophin pathway in metastasis, PNI, and pain.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Bucais / Carcinoma de Células Escamosas / Neoplasias de Cabeça e Pescoço Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Adv Biol (Weinh) Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Bucais / Carcinoma de Células Escamosas / Neoplasias de Cabeça e Pescoço Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Adv Biol (Weinh) Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos