Vascular Cell Adhesion Molecule 1 Predicts Cancer-Free Survival in Clear Cell Renal Carcinoma Patients

Shioi, Koichi; Komiya, Atsushi; Hattori, Kéiko; Huang, Ying; Sano, Futoshi; Murakami, Takayuki; Nakaigawa, Noboru; Kishida, Takeshi; Kubota, Yoshinobu; Nagashima, Yoji; Yao, Masahiro

doi:10.1158/1078-0432.ccr-06-1737

Cited by 49 publications

(41 citation statements)

References 46 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our in vitro adhesion assays indicate that this diminished recruitment of immune cells is directly mediated by Egfl7 through the downregulation of endothelial adhesion molecules. The downregulation of endothelial adhesion molecules in tumors (12)(13)(14)(15) and in human cancers (12,14,26) had already been observed. Egfl7 favors tumor escape from immunity by downregulating the expression of endothelial adhesion molecules through mechanisms that are still elusive.…”

Section: Discussionmentioning

confidence: 92%

Egfl7 Promotes Tumor Escape from Immunity by Repressing Endothelial Cell Activation

et al. 2011

View full text Add to dashboard Cite

Downregulating the leukocyte adhesion molecules expressed by endothelial cells that line tumor blood vessels can limit the entry of immune effector cells into the tumor mass, thereby contributing to tumoral immune escape. Egfl7 (also known as VE-statin) is a secreted protein specifically expressed by endothelial cells in normal tissues and by cancer cells in various human tumors. High levels of Egfl7 correlate with higher tumor grade and poorer prognosis. Here we show that expression of Egfl7 in breast and lung carcinoma cells accelerates tumor growth and metastasis in immunocompetent mice but not in immunodeficient mice. Tumors expressing Egfl7 were infiltrated relatively poorly by immune cells and were characterized by reduced levels of immunostimulatory cytokines ] and fewer endothelial adhesion molecules [intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)]. In vitro studies revealed that Egfl7 inhibited the expression of leukocyte adhesion molecules by endothelial cells, preventing lymphocyte adhesion. In contrast, Egfl7 did not exert any effects on immune cell activation. Human breast cancer lesions expressing high levels of Egfl7 also expressed less ICAM-1 and VCAM-1 in their blood vessels, also indicating an inverse correlation between expression levels of Egfl7 and IFN-g. Thus, Egfl7 expression in tumors promotes tumor progression by reducing the expression of endothelial molecules that mediate immune cell infiltration. Our findings highlight a novel mechanism through which tumors escape immune control. Cancer Res; 71(23); 7176-86. Ó2011 AACR.

show abstract

Section: Discussionmentioning

confidence: 92%

Egfl7 Promotes Tumor Escape from Immunity by Repressing Endothelial Cell Activation

et al. 2011

View full text Add to dashboard Cite

show abstract

“…38 Additionally, the upregulation of VCAM-1 and its prognostic significance have been reported in several human malignances, including RCC, where it was associated with improved survival for patients with advanced mRCC. 39 Following these observations, we analyzed the differential distribution of T-cell subsets in the spleen, mediastinal lymph nodes and the metastatic lung. Interestingly, ES gene therapy induced a significant increase in both T CD4 and CD8 cells in the lymph nodes and spleen, suggesting that ES may facilitate cell survival or clonal expansion.…”

Section: Discussionmentioning

confidence: 99%

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

et al. 2012

View full text Add to dashboard Cite

One of the greatest challenges in urological oncology is renal cell carcinoma (RCC), which is the third leading cause of death in genitourinary cancers. RCCs are highly vascularized and respond positively to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the potential of ES-based antiangiogenic therapy to activate tumor-associated endothelial cells in metastatic RCC (mRCC). Balb/c-bearing Renca cells were treated with NIH/3T3-LendSN or, as a control, with NIH/3T3-LXSN cells. The T-cell subsets and lymphocyte populations of tumors, mediastinal lymph nodes and the spleen were assessed by flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was assessed by real-time PCR, flow cytometry and immunohistochemistry analysis. ES gene therapy led to an increase in the percentage of infiltrating CD4-interferon (IFN)-g cells (Po0.05), CD8-IFN-g cells (Po0.01) and CD49b-tumor necrosis factor-a cells (Po0.01). In addition, ES therapy caused an increase at the mRNA level of ICAM-1 (1.4-fold; Po0.01) and VCAM-1 (1.5-fold) (control vs treated group; Po0.001). Through flow cytometry, we found a significant increase in the CD34/ICAM-1 cells (8.1-fold; Po0.001) and CD34/VCAM-1 cells (1.6-fold; Po0.05). ES gene therapy induced a significant increase in both T CD4 and CD8 cells in the lymph nodes and the spleen, suggesting that ES therapy may facilitate cell survival or clonal expansion. CD49b cells were also present in increased quantities in all of these organs. In this study, we demonstrate an antitumor inflammatory effect of ES in an mRCC model, and this effect is mediated by an increase in ICAM-1 and VCAM-1 expression in tumor-associated endothelial cells.

show abstract

“…Thus, increasing attention is focused on identifying novel molecules that are differentially expressed and/or play a key role in lung cancer cell invasion. Although the roles of VCAM-1 have been reported in several types of cancer [13][14][15][16][17][18], the roles of VCAM-1 in lung cancer have not yet been elucidated. More specifically, the role of the VCAM-1-D6 domain and its potential as a therapeutic target in lung cancer have not been explored.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Sixth Ig-like Domain of VCAM-1 as a Novel Therapeutic Target in Lung Cancer Cell Invasion

Kim

Jang

Park

et al. 2017

Preprint

View full text Add to dashboard Cite

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

show abstract

Vascular Cell Adhesion Molecule 1 Predicts Cancer-Free Survival in Clear Cell Renal Carcinoma Patients

Cited by 49 publications

References 46 publications

Egfl7 Promotes Tumor Escape from Immunity by Repressing Endothelial Cell Activation

Egfl7 Promotes Tumor Escape from Immunity by Repressing Endothelial Cell Activation

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

Identification of the Sixth Ig-like Domain of VCAM-1 as a Novel Therapeutic Target in Lung Cancer Cell Invasion

Contact Info

Product

Resources

About