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Defining the Extracellular Matrix of Rhabdomyosarcoma

Authors :
Ayeza Bajwa
J Steffan Bond
Charles Keller
Sergei P. Boudko
Sakir H. Gultekin
Atiya Mansoor
Megan M. Cleary
Teagan P. Settelmeyer
Christopher P. Hartley
Noah E. Berlow
Melvin Lathara
Hans Peter Bächinger
Elena Pokidysheva
Takako Sasaki
Jack F. Shern
Narendra Bharathy
Xiaolei Lian
Ganapati Srinivasa
Source :
Frontiers in Oncology, Vol 11 (2021), Frontiers in Oncology
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

Abstract

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.

Details

Language :
English
Volume :
11
Database :
OpenAIRE
Journal :
Frontiers in Oncology
Accession number :
edsair.doi.dedup.....422209340e2ad410e025606fd7c5bebe