Thrombospondin-1 in a Murine Model of Colorectal Carcinogenesis.
Colorectal Cancer (CRC) is one of the late complications observed in patients suffering from inflammatory bowel diseases (IBD). Carcinogenesis is promoted by persistent chronic inflammation occurring in IBD. Understanding the mechanisms involved is essential in order to ameliorate inflammation and p...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0139918&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850189134758412288 |
|---|---|
| author | Zenaida P Lopez-Dee Sridar V Chittur Hiral Patel Aleona Chinikaylo Brittany Lippert Bhumi Patel Jack Lawler Linda S Gutierrez |
| author_facet | Zenaida P Lopez-Dee Sridar V Chittur Hiral Patel Aleona Chinikaylo Brittany Lippert Bhumi Patel Jack Lawler Linda S Gutierrez |
| author_sort | Zenaida P Lopez-Dee |
| collection | DOAJ |
| description | Colorectal Cancer (CRC) is one of the late complications observed in patients suffering from inflammatory bowel diseases (IBD). Carcinogenesis is promoted by persistent chronic inflammation occurring in IBD. Understanding the mechanisms involved is essential in order to ameliorate inflammation and prevent CRC. Thrombospondin 1 (TSP-1) is a multidomain glycoprotein with important roles in angiogenesis. The effects of TSP-1 in colonic tumor formation and growth were analyzed in a model of inflammation-induced carcinogenesis. WT and TSP-1 deficient mice (TSP-1-/-) of the C57BL/6 strain received a single injection of azoxymethane (AOM) and multiple cycles of dextran sodium sulfate (DSS) to induce chronic inflammation-related cancers. Proliferation and angiogenesis were histologically analyzed in tumors. The intestinal transcriptome was also analyzed using a gene microarray approach. When the area containing tumors was compared with the entire colonic area of each mouse, the tumor burden was decreased in AOM/DSS-treated TSP-1-/- versus wild type (WT) mice. However, these lesions displayed more angiogenesis and proliferation rates when compared with the WT tumors. AOM-DSS treatment of TSP-1-/- mice resulted in significant deregulation of genes involved in transcription, canonical Wnt signaling, transport, defense response, regulation of epithelial cell proliferation and metabolism. Microarray analyses of these tumors showed down-regulation of 18 microRNAs in TSP-1-/- tumors. These results contribute new insights on the controversial role of TSP-1 in cancer and offer a better understanding of the genetics and pathogenesis of CRC. |
| format | Article |
| id | doaj-art-33637de2ff60422d8b869aa82d36b2e0 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-33637de2ff60422d8b869aa82d36b2e02025-08-20T02:15:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e013991810.1371/journal.pone.0139918Thrombospondin-1 in a Murine Model of Colorectal Carcinogenesis.Zenaida P Lopez-DeeSridar V ChitturHiral PatelAleona ChinikayloBrittany LippertBhumi PatelJack LawlerLinda S GutierrezColorectal Cancer (CRC) is one of the late complications observed in patients suffering from inflammatory bowel diseases (IBD). Carcinogenesis is promoted by persistent chronic inflammation occurring in IBD. Understanding the mechanisms involved is essential in order to ameliorate inflammation and prevent CRC. Thrombospondin 1 (TSP-1) is a multidomain glycoprotein with important roles in angiogenesis. The effects of TSP-1 in colonic tumor formation and growth were analyzed in a model of inflammation-induced carcinogenesis. WT and TSP-1 deficient mice (TSP-1-/-) of the C57BL/6 strain received a single injection of azoxymethane (AOM) and multiple cycles of dextran sodium sulfate (DSS) to induce chronic inflammation-related cancers. Proliferation and angiogenesis were histologically analyzed in tumors. The intestinal transcriptome was also analyzed using a gene microarray approach. When the area containing tumors was compared with the entire colonic area of each mouse, the tumor burden was decreased in AOM/DSS-treated TSP-1-/- versus wild type (WT) mice. However, these lesions displayed more angiogenesis and proliferation rates when compared with the WT tumors. AOM-DSS treatment of TSP-1-/- mice resulted in significant deregulation of genes involved in transcription, canonical Wnt signaling, transport, defense response, regulation of epithelial cell proliferation and metabolism. Microarray analyses of these tumors showed down-regulation of 18 microRNAs in TSP-1-/- tumors. These results contribute new insights on the controversial role of TSP-1 in cancer and offer a better understanding of the genetics and pathogenesis of CRC.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0139918&type=printable |
| spellingShingle | Zenaida P Lopez-Dee Sridar V Chittur Hiral Patel Aleona Chinikaylo Brittany Lippert Bhumi Patel Jack Lawler Linda S Gutierrez Thrombospondin-1 in a Murine Model of Colorectal Carcinogenesis. PLoS ONE |
| title | Thrombospondin-1 in a Murine Model of Colorectal Carcinogenesis. |
| title_full | Thrombospondin-1 in a Murine Model of Colorectal Carcinogenesis. |
| title_fullStr | Thrombospondin-1 in a Murine Model of Colorectal Carcinogenesis. |
| title_full_unstemmed | Thrombospondin-1 in a Murine Model of Colorectal Carcinogenesis. |
| title_short | Thrombospondin-1 in a Murine Model of Colorectal Carcinogenesis. |
| title_sort | thrombospondin 1 in a murine model of colorectal carcinogenesis |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0139918&type=printable |
| work_keys_str_mv | AT zenaidaplopezdee thrombospondin1inamurinemodelofcolorectalcarcinogenesis AT sridarvchittur thrombospondin1inamurinemodelofcolorectalcarcinogenesis AT hiralpatel thrombospondin1inamurinemodelofcolorectalcarcinogenesis AT aleonachinikaylo thrombospondin1inamurinemodelofcolorectalcarcinogenesis AT brittanylippert thrombospondin1inamurinemodelofcolorectalcarcinogenesis AT bhumipatel thrombospondin1inamurinemodelofcolorectalcarcinogenesis AT jacklawler thrombospondin1inamurinemodelofcolorectalcarcinogenesis AT lindasgutierrez thrombospondin1inamurinemodelofcolorectalcarcinogenesis |