The role of Glial cell derived neurotrophic factor in head and neck cancer.
Glial cell-derived neurotrophic factor (GDNF) is reported to promote the survival of neurons and salivary gland regeneration after radiation damage. This study investigated the effect of GDNF on cell migration, growth, and response to radiation in preclinical models of head and neck squamous cell ca...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0229311 |
| _version_ | 1818667179121311744 |
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| author | Hongbin Cao Qian He Rie von Eyben Joshua Bloomstein Dhanya K Nambiar Vignesh Viswanathan Sonya Aggarwal Shirley Kwok Rachel Liang Amanda Jeanette Koong James S Lewis Christina Kong Nan Xiao Quynh-Thu Le |
| author_facet | Hongbin Cao Qian He Rie von Eyben Joshua Bloomstein Dhanya K Nambiar Vignesh Viswanathan Sonya Aggarwal Shirley Kwok Rachel Liang Amanda Jeanette Koong James S Lewis Christina Kong Nan Xiao Quynh-Thu Le |
| author_sort | Hongbin Cao |
| collection | DOAJ |
| description | Glial cell-derived neurotrophic factor (GDNF) is reported to promote the survival of neurons and salivary gland regeneration after radiation damage. This study investigated the effect of GDNF on cell migration, growth, and response to radiation in preclinical models of head and neck squamous cell carcinoma (HNSCC) and correlated GDNF expression to treatment outcomes in HNSCC patients. Our ultimate goal is to determine whether systemic administration of GDNF at high dose is safe for the management of hyposalivation or xerostomia in HNSCC patients. Three HPV-positive and three HPV-negative cell lines were examined for cell migration, growth, and clonogenic survival in vitro and tumor growth assay in vivo. Immunohistochemical staining of GDNF, its receptors GFRα1 and its co-receptor RET was performed on two independent HNSCC tissue microarrays (TMA) and correlated to treatment outcomes. Results showed that GDNF only enhanced cell migration in two HPV-positive cells at supra-physiologic doses, but not in HPV-negative cells. GDNF did not increase cell survival in the tested cell lines post-irradiation. Likewise, GDNF treatment affected neither tumor growth in vitro nor response to radiation in xenografts in two HPV-positive and two HPV-negative HNSCC models. High stromal expression of GDNF protein was associated with worse overall survival in HPV-negative HNSCC on multivariate analysis in a combined cohort of patients from Stanford University (n = 82) and Washington University (n = 189); however, the association between GDNF gene expression and worse survival was not confirmed in a separate group of HPV-negative HNSCC patients identified from the Cancer Genome Atlas (TCGA) database. Based on these data, we do not believe that GNDF is a safe systemic treatment to prevent or treat xerostomia in HNSCC and a local delivery approach such as intraglandular injection needs to be explored. |
| first_indexed | 2024-12-17T06:16:18Z |
| format | Article |
| id | doaj.art-51c99b646dd34a418aed18e5b84f01b3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T06:16:18Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-51c99b646dd34a418aed18e5b84f01b32022-12-21T22:00:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01152e022931110.1371/journal.pone.0229311The role of Glial cell derived neurotrophic factor in head and neck cancer.Hongbin CaoQian HeRie von EybenJoshua BloomsteinDhanya K NambiarVignesh ViswanathanSonya AggarwalShirley KwokRachel LiangAmanda Jeanette KoongJames S LewisChristina KongNan XiaoQuynh-Thu LeGlial cell-derived neurotrophic factor (GDNF) is reported to promote the survival of neurons and salivary gland regeneration after radiation damage. This study investigated the effect of GDNF on cell migration, growth, and response to radiation in preclinical models of head and neck squamous cell carcinoma (HNSCC) and correlated GDNF expression to treatment outcomes in HNSCC patients. Our ultimate goal is to determine whether systemic administration of GDNF at high dose is safe for the management of hyposalivation or xerostomia in HNSCC patients. Three HPV-positive and three HPV-negative cell lines were examined for cell migration, growth, and clonogenic survival in vitro and tumor growth assay in vivo. Immunohistochemical staining of GDNF, its receptors GFRα1 and its co-receptor RET was performed on two independent HNSCC tissue microarrays (TMA) and correlated to treatment outcomes. Results showed that GDNF only enhanced cell migration in two HPV-positive cells at supra-physiologic doses, but not in HPV-negative cells. GDNF did not increase cell survival in the tested cell lines post-irradiation. Likewise, GDNF treatment affected neither tumor growth in vitro nor response to radiation in xenografts in two HPV-positive and two HPV-negative HNSCC models. High stromal expression of GDNF protein was associated with worse overall survival in HPV-negative HNSCC on multivariate analysis in a combined cohort of patients from Stanford University (n = 82) and Washington University (n = 189); however, the association between GDNF gene expression and worse survival was not confirmed in a separate group of HPV-negative HNSCC patients identified from the Cancer Genome Atlas (TCGA) database. Based on these data, we do not believe that GNDF is a safe systemic treatment to prevent or treat xerostomia in HNSCC and a local delivery approach such as intraglandular injection needs to be explored.https://doi.org/10.1371/journal.pone.0229311 |
| spellingShingle | Hongbin Cao Qian He Rie von Eyben Joshua Bloomstein Dhanya K Nambiar Vignesh Viswanathan Sonya Aggarwal Shirley Kwok Rachel Liang Amanda Jeanette Koong James S Lewis Christina Kong Nan Xiao Quynh-Thu Le The role of Glial cell derived neurotrophic factor in head and neck cancer. PLoS ONE |
| title | The role of Glial cell derived neurotrophic factor in head and neck cancer. |
| title_full | The role of Glial cell derived neurotrophic factor in head and neck cancer. |
| title_fullStr | The role of Glial cell derived neurotrophic factor in head and neck cancer. |
| title_full_unstemmed | The role of Glial cell derived neurotrophic factor in head and neck cancer. |
| title_short | The role of Glial cell derived neurotrophic factor in head and neck cancer. |
| title_sort | role of glial cell derived neurotrophic factor in head and neck cancer |
| url | https://doi.org/10.1371/journal.pone.0229311 |
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