Intercellular adhesion molecule-1 mediates murine colon adenocarcinoma invasion

Abstract

Background Intercellular adhesion molecule-1 (ICAM-1) modulates cell–cell adhesion and is a receptor for cognate ligands on leukocytes. Upregulation of ICAM-1 has been demonstrated in malignant transformation of adenomas and is associated with poor prognosis for many malignancies. ICAM-1 is upregulated on the invasive front of pancreatic metastases and melanomas. These data suggest that the upregulated ICAM-1 expression promotes malignant progression. We hypothesize that the downregulation of ICAM-1 will mitigate tumor progression. Methods Mouse colon adenocarcinoma cells (MC38) were evaluated for the expression of ICAM-1 using Western immunoblot analysis. Short hairpin RNA (shRNA) transduction was used to downregulate ICAM-1. Tumor invasion determined via a modified Boyden chamber was used as a surrogate of tumor progression examining MC38 cells, MC38 ICAM-1 knockdowns, and MC38 transduced with vehicle control. The cells were cultured in full media for 24 h and serum-starved for 24 h. A total of 5 × 104 cells were plated and allowed to migrate for 24 h using full media with 10% fetal bovine serum as a chemoattractant. Inserts were fixed and stained with crystal violet. Blinded investigators counted the cells using a stereomicroscope. Statistical analysis was performed by analysis of variance with Fischer protected least significant difference and a P value of <0.05 was considered statistically significant. Results ICAM-1 was constitutively expressed on MC38 cells. Transduction with anti–ICAM-1 shRNA vector downregulated ICAM-1 protein expression by 30% according to the Western blot analysis (P < 0.03) and decreased ICAM-1 messenger RNA expression by 70% according to the reverse transcription–polymerase chain reaction. shRNA knockdown cells had a significant reduction in invasion >45% (P < 0.03). There were no significant differences between the invasion rates of MC38 and MC38 vehicle controls. Conclusions Downregulation of ICAM-1 mitigates MC38 invasion. These data suggest that targeted downregulation of tumor ICAM-1 is a potential therapeutic target.

Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer

“…Hyperinsulinemia increases colon cancer cell resistance to 5-fluorouracil [ 31 ], and oxaliplatin chemotherapy [ 31 , 32 ], and exposure to insulin promotes colonic tumor multiplicity [ 33 ]. sICAM-1 is associated with obesity and hyperinsulinemia [ 34 ], and exposure to sICAM-1 stimulates tumor growth [ 35 ], and the inhibition of sICAM-1 attenuates colonic tumor cell invasion [ 36 ]. These in vivo and preclinical data are supported by prospective cohort studies that suggest higher BMI and visceral obesity [ 16 , 18 ], hyperinsulinemia [ 17 ], and elevated sICAM-1 [ 37 ] are associated with recurrence and survival among patients with colon cancer.…”

Downregulation of human intercellular adhesion molecule-1 attenuates the metastatic ability in human breast cancer cell lines

“…Previous research has shown that upregulation of ICAM-1 has been demonstrated in different malignant tumors including liver cancer, esophageal cancer, renal cell carcinoma, squamous carcinoma, gastric cancer or pancreatic cancer and associated with poor prognosis (14,15,(19)(20)(21)(22).Under inflammatory environment, TGF (transforming growth factor) promoted osteosarcoma cell metastasis through the increasement of ICAM-1 by Akt signal pathway (23). Downregulation of ICAM-1 by short hairpin RNA (shRNA) transduction methods mitigated mouse colon cancer cell MC38 invasion ability (24). Proto oncogene K-ras could increase ICAM-1 expression in pancreatic acinar cells and the formation of precancerous lesions (25).…”

Dose-response Effects of Aerobic Exercise Among Colon Cancer Survivors: A Randomized Phase II Trial

“…The biologic pathways through which exercise may reduce the risk for disease recurrence and premature mortality have not been elucidated. Endothelial cell-adhesion molecules including sICAM-1 and sVCAM-1 have emerged as therapeutic targets, 22,23 given their implication in promoting the growth of existing micro-metastases and the formation of new micro-metastases through circulating tumor cell differentiation, cell-cell adhesion and dissemination via activation of the PI3K-Akt-mTOR pathway. 16 We hypothesized that exercise would reduce sICAM-1 and sVCAM-1.…”

“…16 Concentrations of sICAM-1 and sVCAM-1 increase with disease stage, 17,18 and elevated concentrations of sICAM-1 and sVCAM-1 are independently associated with disease recurrence and premature death among colon cancer survivors. 17–21 sICAM-1 and sVCAM-1 have been recommended as therapeutic targets, 22,23 and represent novel pathways through which exercise may reduce the risk of disease recurrence among colon cancer survivors.…”