LFA-1 Expression in a Series of Colorectal Adenocarcinomas

Papas, Maria G; Papanikolaou, Ioannis S.; Karamitopoulou, Evanthia; Delicha, Eumorphia Maria; Adler, Andreas; Triantafyllou, Konstantinos; Thomopoulou, Georgia-Eleni; Patsouris, Efstratios; Lazaris, Andreas C.

doi:10.1007/s12029-011-9341-6

Cited by 7 publications

(6 citation statements)

References 14 publications

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“…Integrins are also important in promoting cell survival by preventing anoikis, which is apoptosis induced by anchorage-dependent cells detaching from the surrounding ECM (23,24). There has been accumulating evidence showing that integrins β-2 and β-3 have a relationship with cancer progression and migration, including HCC (25–31). For example, Li et al reported that the downregulation of integrin β-3 in small cell lung cancer cells reduced cell migration/invasion and induced apoptosis (30).…”

Section: Discussionmentioning

confidence: 99%

Collagen triple helix repeat containing 1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation and motility

Tameda

Sugimoto

Shiraki

et al. 2014

International Journal of Oncology

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Although several therapeutic options are available for hepatocellular carcinoma (HCC), the outcome is still very poor. One reason is the complexity of signal transduction in the pathogenesis of HCC. The aim of this study was to identify new HCC-related genes and to investigate the functions of these genes in the pathogenesis and progression of HCC. Whole genomes of 15 surgically resected HCC specimens were examined for copy number alterations with comparative genomic hybridization. Gene expression was compared between HCC and normal liver tissues. The roles of the new genes in the progression of HCC were studied using cultured cell lines. Copy number gain in chromosome 8q was detected in 53% of HCC tissues examined. The gene that coded for collagen triple helix repeat containing 1 (CTHRC1), located at chromosome 8q22.3, was overexpressed in HCC compared with normal or liver cirrhosis tissues and identified as a new HCC-related gene. CTHRC1 deletion with short hairpin RNA significantly reduced proliferation, migration and invasion of HepG2 and Huh7 cells. In addition, mRNA of integrins β-2 and β-3 was downregulated, with deletion of CTHRC1 in these cells. Immunohistochemical staining on resected HCC tissues showing positive staining areas for CTHRC1 was significantly greater in poorly-differentiated HCC compared with well-differentiated HCC. Moreover, some cases showed strong staining for CTHRC1 in invasive areas of HCC. CTHRC1 has the potential to be a new biomarker for the aggressive HCC, and to be a new therapeutic target in treating HCC.

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Section: Discussionmentioning

confidence: 99%

Collagen triple helix repeat containing 1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation and motility

Tameda

Sugimoto

Shiraki

et al. 2014

International Journal of Oncology

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“…To elucidate the mechanisms, the team performed a qRT-PCR array and the experiment result demonstrated that integrin β underwent great changes after the knock down of CTHRC1. It has been reported that integrin β2/β3 are related with tumor metastasis 51-57. Integrins, composed by α- and β-subunits, are one type of transmembrane receptors.…”

Section: The Role Of Cthrc1 In Multi-signaling Pathwaysmentioning

confidence: 99%

Multidimensional Roles of Collagen Triple Helix Repeat Containing 1 (CTHRC1) in Malignant Cancers

et al. 2016

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Tumor is one of the principal diseases that seriously threaten human health. Insight into sensitive cancer markers may open a new avenue for the early diagnosis and treatment of this disease. CTHRC1 has been identified as a cancer-related gene. It is a secretory glycoprotein that possesses multidimensional roles associated with wound repair, bone remodeling, hepatocytes fibrosis, adipose tissue formation, and so on. Our previous studies and numerous reports from other researchers have revealed that the ascended expression of CTHRC1 tends to go hand in hand with tumorigenesis, proliferation, invasion and metastasis in various human malignancies through a series of molecular mechanisms and signaling pathways. However, the detailed pathogenic mechanisms of CTHRC1 overexpression in human malignant cancers are not yet clear. Here, we shall focus our description on the functions, expression profile in several representative malignant tumors and a number of molecular mechanisms and signaling pathways involved with CTHRC1. This introductory discussion of CTHRC1 will serve as a reference for further research in understanding this intriguing cancer-related protein.

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“…Lymphocyte Function Associated Antigen (LFA)-1 (CD11a/CD18 or α L β 2 ) is a heterodimeric protein of the integrin family expressed on the surface of nearly all leukocytes [ 5 ] and recently described on a variety of tumor cells [ 1 , 6 , 7 ] including colorectal cancer cells [ 8 , 9 ]. LFA-1 is the main ligand for intercellular adhesion molecule (ICAM)-1 [ 10 , 11 ] to which the integrin binds with the highest affinity.…”

Section: Introductionmentioning

confidence: 99%

Decreased expression of the β2 integrin on tumor cells is associated with a reduction in liver metastasis of colorectal cancer in mice

et al. 2017

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BackgroundLymphocyte Function-Associated Antigen-1 (LFA-1; CD18/CD11a) is one of the main adhesion molecules used by immune cells to infiltrate the liver under inflammatory conditions. Recently, the expression of this integrin has also been reported on several solid tumors, including colorectal cancer. However, its functional role in the metastatic progression to the liver remains unknown. Using in vitro assays and an experimental orthotopic in vivo model of liver metastasis, we aimed to elucidate the role of tumor LFA-1 in the metastatic progression by means of the partial depletion of the β2 subunit of LFA-1, required for integrin activation, firm adhesion and signaling.MethodsTo do so, we evaluated the effects of β2 reduction on the murine colon carcinoma C26 cell line on their pro-metastatic features in vitro and their metastatic potential in vivo in a mouse model of colon carcinoma metastasis to the liver.ResultsThe reduction in β2 integrin expression correlated with a slower proliferation, and a reduced adhesion and migration of C26 cells in an in vitro setting. Additionally, tumor cells with a reduced in β2 integrin expression were unable to activate the liver sinusoidal endothelial cells (LSECs). This resulted in a recovery of the cytotoxic potential of liver lymphocytes which is compromised by LSECs activated by C26 cells. This was related to the abrogation of RNA expression of inflammatory and angiogenic cytokines by C26 cells after their activation with sICAM-1, the main ligand of β2αL. Furthermore, in vivo tumor cell retention and metastasis were profoundly reduced, along with a decrease in the recruitment and infiltration of myeloid derived suppressor cells (MDSCs) and lymphocytes to the liver.ConclusionTaken together, our findings uncovered the modulatory role for the tumor β2 subunit of the LFA-1 integrin in the metastatic progression of colorectal cancer to the liver by impairing activation of liver endothelium and thus, the local immune response in the liver. Besides, this integrin also showed to be critical in vivo for tumor cell retention, cytokine release, leukocyte recruitment and metastasis development. These data support a therapeutical potential of the integrin LFA-1 as a target for the treatment of colorectal liver metastasis.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3823-2) contains supplementary material, which is available to authorized users.

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LFA-1 Expression in a Series of Colorectal Adenocarcinomas

Abstract: The positive association of LFA-1 expression in mLNs when the primary tumor site is also LFA-1(+) could imply an adaptation advantage of this specific cellular clone to its micro-environment, predisposing it to creation of mLNs, pointing to a role for LFA-1 in creation of mLNs in CRC.

Cited by 7 publications

References 14 publications

Collagen triple helix repeat containing 1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation and motility

Collagen triple helix repeat containing 1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation and motility

Multidimensional Roles of Collagen Triple Helix Repeat Containing 1 (CTHRC1) in Malignant Cancers

Decreased expression of the β2 integrin on tumor cells is associated with a reduction in liver metastasis of colorectal cancer in mice

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