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Defining the Extracellular Matrix of Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood with a propensity to metastasize. Current treatment for patients with RMS includes conventional systemic chemotherapy, radiation therapy, and surgical resection; nevertheless, little to no improvement in long term survival ha...

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Autores principales: Lian, Xiaolei, Bond, J. Steffan, Bharathy, Narendra, Boudko, Sergei P., Pokidysheva, Elena, Shern, Jack F., Lathara, Melvin, Sasaki, Takako, Settelmeyer, Teagan, Cleary, Megan M., Bajwa, Ayeza, Srinivasa, Ganapati, Hartley, Christopher P., Bächinger, Hans Peter, Mansoor, Atiya, Gultekin, Sakir H., Berlow, Noah E., Keller, Charles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942227/
https://www.ncbi.nlm.nih.gov/pubmed/33708626
http://dx.doi.org/10.3389/fonc.2021.601957
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author Lian, Xiaolei
Bond, J. Steffan
Bharathy, Narendra
Boudko, Sergei P.
Pokidysheva, Elena
Shern, Jack F.
Lathara, Melvin
Sasaki, Takako
Settelmeyer, Teagan
Cleary, Megan M.
Bajwa, Ayeza
Srinivasa, Ganapati
Hartley, Christopher P.
Bächinger, Hans Peter
Mansoor, Atiya
Gultekin, Sakir H.
Berlow, Noah E.
Keller, Charles
author_facet Lian, Xiaolei
Bond, J. Steffan
Bharathy, Narendra
Boudko, Sergei P.
Pokidysheva, Elena
Shern, Jack F.
Lathara, Melvin
Sasaki, Takako
Settelmeyer, Teagan
Cleary, Megan M.
Bajwa, Ayeza
Srinivasa, Ganapati
Hartley, Christopher P.
Bächinger, Hans Peter
Mansoor, Atiya
Gultekin, Sakir H.
Berlow, Noah E.
Keller, Charles
author_sort Lian, Xiaolei
collection PubMed
description Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood with a propensity to metastasize. Current treatment for patients with RMS includes conventional systemic chemotherapy, radiation therapy, and surgical resection; nevertheless, little to no improvement in long term survival has been achieved in decades—underlining the need for target discovery and new therapeutic approaches to targeting tumor cells or the tumor microenvironment. To evaluate cross-species sarcoma extracellular matrix production, we have used murine models which feature knowledge of the myogenic cell-of-origin. With focus on the RMS/undifferentiated pleomorphic sarcoma (UPS) continuum, we have constructed tissue microarrays of 48 murine and four human sarcomas to analyze expression of seven different collagens, fibrillins, and collagen-modifying proteins, with cross-correlation to RNA deep sequencing. We have uncovered that RMS produces increased expression of type XVIII collagen alpha 1 (COL18A1), which is clinically associated with decreased long-term survival. We have also identified significantly increased RNA expression of COL4A1, FBN2, PLOD1, and PLOD2 in human RMS relative to normal skeletal muscle. These results complement recent studies investigating whether soft tissue sarcomas utilize collagens, fibrillins, and collagen-modifying enzymes to alter the structural integrity of surrounding host extracellular matrix/collagen quaternary structure resulting in improved ability to improve the ability to invade regionally and metastasize, for which therapeutic targeting is possible.
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spelling pubmed-79422272021-03-10 Defining the Extracellular Matrix of Rhabdomyosarcoma Lian, Xiaolei Bond, J. Steffan Bharathy, Narendra Boudko, Sergei P. Pokidysheva, Elena Shern, Jack F. Lathara, Melvin Sasaki, Takako Settelmeyer, Teagan Cleary, Megan M. Bajwa, Ayeza Srinivasa, Ganapati Hartley, Christopher P. Bächinger, Hans Peter Mansoor, Atiya Gultekin, Sakir H. Berlow, Noah E. Keller, Charles Front Oncol Oncology Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood with a propensity to metastasize. Current treatment for patients with RMS includes conventional systemic chemotherapy, radiation therapy, and surgical resection; nevertheless, little to no improvement in long term survival has been achieved in decades—underlining the need for target discovery and new therapeutic approaches to targeting tumor cells or the tumor microenvironment. To evaluate cross-species sarcoma extracellular matrix production, we have used murine models which feature knowledge of the myogenic cell-of-origin. With focus on the RMS/undifferentiated pleomorphic sarcoma (UPS) continuum, we have constructed tissue microarrays of 48 murine and four human sarcomas to analyze expression of seven different collagens, fibrillins, and collagen-modifying proteins, with cross-correlation to RNA deep sequencing. We have uncovered that RMS produces increased expression of type XVIII collagen alpha 1 (COL18A1), which is clinically associated with decreased long-term survival. We have also identified significantly increased RNA expression of COL4A1, FBN2, PLOD1, and PLOD2 in human RMS relative to normal skeletal muscle. These results complement recent studies investigating whether soft tissue sarcomas utilize collagens, fibrillins, and collagen-modifying enzymes to alter the structural integrity of surrounding host extracellular matrix/collagen quaternary structure resulting in improved ability to improve the ability to invade regionally and metastasize, for which therapeutic targeting is possible. Frontiers Media S.A. 2021-02-23 /pmc/articles/PMC7942227/ /pubmed/33708626 http://dx.doi.org/10.3389/fonc.2021.601957 Text en Copyright © 2021 Lian, Bond, Bharathy, Boudko, Pokidysheva, Shern, Lathara, Sasaki, Settelmeyer, Cleary, Bajwa, Srinivasa, Hartley, Bächinger, Mansoor, Gultekin, Berlow and Keller http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Lian, Xiaolei
Bond, J. Steffan
Bharathy, Narendra
Boudko, Sergei P.
Pokidysheva, Elena
Shern, Jack F.
Lathara, Melvin
Sasaki, Takako
Settelmeyer, Teagan
Cleary, Megan M.
Bajwa, Ayeza
Srinivasa, Ganapati
Hartley, Christopher P.
Bächinger, Hans Peter
Mansoor, Atiya
Gultekin, Sakir H.
Berlow, Noah E.
Keller, Charles
Defining the Extracellular Matrix of Rhabdomyosarcoma
title Defining the Extracellular Matrix of Rhabdomyosarcoma
title_full Defining the Extracellular Matrix of Rhabdomyosarcoma
title_fullStr Defining the Extracellular Matrix of Rhabdomyosarcoma
title_full_unstemmed Defining the Extracellular Matrix of Rhabdomyosarcoma
title_short Defining the Extracellular Matrix of Rhabdomyosarcoma
title_sort defining the extracellular matrix of rhabdomyosarcoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942227/
https://www.ncbi.nlm.nih.gov/pubmed/33708626
http://dx.doi.org/10.3389/fonc.2021.601957
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