Dinh Quang Truong1, Ban Tran Ho2,3, Gia-Cac Chau4, Dinh Khai Truong2,3, Thuy Thi Thanh Pham5, Akira Nakagawara6, Chi-Bao Bui1,7,8. 1. City Children's Hospital, Ho Chi Minh City, Vietnam. 2. Department of Paediatric Surgery, Faculty of Medicine, University of medicine and pharmacy at Hochiminh city, Vietnam. 3. Children Hospital 2, Ho Chi Minh City, Vietnam. 4. School of Medicine, Sungkyunkwan University, Suwon, Korea. 5. Epigenetic Unit, DNA Medical Technology, Ho Chi Minh City, Vietnam. 6. Division of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba, Japan. 7. Vietnam National University Ho Chi Minh city, Ho Chi Minh, Vietnam. 8. School of Medicine, Ho Chi Minh city, Vietnam.
Abstract
BACKGROUND: Neuroblastoma (NB) is among the most common cancers in children. A highly aggressive form of cancer, NB relies on cells in the microenvironment for dissemination particularly cancer associated fibroblast (CAFs). CAFs synthesise the extracellular matrix to create a scaffold for tumor growth thus enabling the carcinogenesis of NB, Collagen, an abundant scaffold protein produced by CAFs, has been implicated in the creation of an optimal tumor microenvironment, however, the expression profile of collagen within NB is not yet known. METHODS: We characterised collagen expression within the tumor-stroma boundary by microarray and confirmed by qRT-PCR and immunohistochemistry. RESULTS: The collagen marker, COL11A1, was also upregulated in NB CD45+ cells and SMA+ CAFs. Furthermore, SMA+ CAFs led to neuroblastoma cell invasion in an in vitro co-culture system which was subsequently attenuated by gene silencing COL11A1. Immunohistochemical staining of clinical tumor samples revealed that high COL11A1 expression in the stroma adjacent to tumour site, significantly associated with advanced cancer stages, age ≥18 months, undifferentiated tumor status, relapse and poor overall survival. CONCLUSION: Collectively, these results suggest that a COL11A1 signature in the NB microenvironment could represent a novel target for therapeutic intervention.
BACKGROUND: Neuroblastoma (NB) is among the most common cancers in children. A highly aggressive form of cancer, NB relies on cells in the microenvironment for dissemination particularly cancer associated fibroblast (CAFs). CAFs synthesise the extracellular matrix to create a scaffold for tumor growth thus enabling the carcinogenesis of NB, Collagen, an abundant scaffold protein produced by CAFs, has been implicated in the creation of an optimal tumor microenvironment, however, the expression profile of collagen within NB is not yet known. METHODS: We characterised collagen expression within the tumor-stroma boundary by microarray and confirmed by qRT-PCR and immunohistochemistry. RESULTS: The collagen marker, COL11A1, was also upregulated in NB CD45+ cells and SMA+ CAFs. Furthermore, SMA+ CAFs led to neuroblastoma cell invasion in an in vitro co-culture system which was subsequently attenuated by gene silencing COL11A1. Immunohistochemical staining of clinical tumor samples revealed that high COL11A1 expression in the stroma adjacent to tumour site, significantly associated with advanced cancer stages, age ≥18 months, undifferentiated tumor status, relapse and poor overall survival. CONCLUSION: Collectively, these results suggest that a COL11A1 signature in the NB microenvironment could represent a novel target for therapeutic intervention.
Entities:
Keywords:
COL11A1; cancer associated fibroblast; collagen; microenvironment; molecular oncology; neuroblastoma