VCAM-1 Gene Editing    

Vascular cell adhesion molecule-1 (VCAM-1), also known as CD106, is a 90-kDa glycoprotein. VCAM-1 is inducible and, most commonly expressed in endothelial cells, however, other cell types such as dendritic cells, tissue macrophages, cancer cells, Kupffer cells, etc. also show expression of VCAM-1 on their surface. Initially, VCAM-1 was detected as a cell adhesion molecule that plays a role in the regulation of inflammation-linked vascular adhesion and transendothelial movement of leukocytes, including T cells and macrophages. In vitro, studies on cytoadherence of P. falciparum isolates taken from infected individuals showing various binding affinities to several human host proteins, for example, CD36, VCAM-1, CR1, ICAM-1, and gC1qR/HABP1/p32 serve as receptor for binding to infected erythrocytes.

Figure 1. Mechanism of VCAM-1–mediated leukocyte adhesion and transendothelial migration across endothelial cells. (Kong D H, et al., 2018)

Role of VCAM-1 in Cancer

In recent years, increasing amounts of evidence show that VCAM-1 is closely related to tumor angiogenesis and metastasis. Yong-Bin et al. reported that VCAM-1-positive tissue has a higher microvessel density than VCAM-1-negative tissue in gastric cancer. Byrne et al. reported that serum VCAM-1 levels are associated with the microvessel density of breast cancer, indicating that serum VCAM-1 may be a surrogate marker of angiogenesis in breast cancer. Other studies have shown that VEGF can upregulate the expression of VCAM-1 expression on endothelial cells. Much attention has been paid to the interaction between VCAM-1 and α4β1 integrin in angiogenesis. For instance, Garmy-Susini et al. first observed that VCAM-1 and α4β1 integrin were individually expressed on vascular smooth muscle cells and endothelial cells in the developing vessels of breast cancer, and found that the administration of an anti-murine VCAM-1 antibody (M/K-2) specifically reduced microvessel formation in Matrigel plug mouse models. In addition, VCAM-1 expression seems to be closely implicated in the metastasis of a variety of cancer cells. For example, through a comparative gene profile analysis of parental MDA-MB-231 breast cancer cells and in vivo isolates exhibiting lung metastatic activity, Minn et al. found that VCAM-1 expression is upregulated in metastatic breast cancer cells to the lungs. Liu et al. found that VCAM-1 expression was related to the clinicopathological grade of gliomas. Moreover, mesothelium VCAM-1 expression was negatively associated with progression-free and overall survival in patients with epithelium ovarian cancers.

VCAM-1 as A Potential Therapeutic Target

Blockade of endothelial VCAM-1 adhesive functions seems to be expected to interfere with cancer diseases. TC or myeloid cell adhesion to the endothelium and for this reason the establishment of metastatic niche could potentially be reduced. However, direct blocking approaches of VCAM-1 by small molecules or antibodies have not been described yet. Therefore, some drugs with miscellaneous indications exhibit anti-adhesive effects on TCs due to a downregulation of VCAM-1 and other CAMs on endothelial cells. Morphine can decrease VCAM-1 expression on HUVECs treated with the supernatant of LPS stimulated colon cancer cells. Resveratrol prevented hepatic melanoma metastasis through attenuation of IL-18 dependent expression of VCAM-1 on sinusoidal endothelial cells.

Although there is no advanced method to directly block VCAM-1, the blockade of VCAM-1 counter receptors VLA-4 and α4β7 is well established in treatment of multiple sclerosis and inflammatory bowel disease by the mAbs natalizumab and vedolizumab. VLA-4 inhibition by small molecules or heparin derivatives are also promising methods currently investigated. In animal trials, natalizumab attenuated multiple myeloma cell growth in the bone marrow microenvironment and prevented osteolysis. In an experimental model of melanoma metastasis, natalizumab reduced the metastatic burden to the lungs. However, inhibition of the VLA-4/VCAM-1 interaction affects the cellular immune response. Therefore, the combination of chemotherapeutic agents with potential VCAM-1 inhibitors could have beneficial effects on metastasis, angiogenesis or lymph node spreading for cancer patients, but it can also have lethal adverse effects.

VCAM-1 Gene Editing Services

CRISPR/Cas9 Platform^CB at Creative Biogene is dedicated to offering comprehensive CRISPR/Cas9 gene editing services and products for academic research, biotech research and pharmaceutical drug discovery. With deep gene editing knowledge and extensive experience in experimental operation and data processing, we help you effectively control VCAM-1 genes knockout/knockin/point mutation in cells or animals via CRISPR/Cas9 technology.

Service	Details	Alternative cell lines or animal species
VCAM-1 Gene Editing Cell Line Generation	gRNA design and synthesis Transfect the cell lines you’re interested Select the high expression cells and sort monoclonal cell Validate the knockout/knockin/point mutation of VCAM-1 by PCR and sequencing Provide cryogenically preserved vials of stable cells and final reports	HEK239T, Hela, HepG2, U87, Ba/F3, CHO, MDA-MB-453, MDA-MB-231NIH3T3, T47D, Neuro2a, MCF7, RKO, K562, RAW264.7, etc.
VCAM-1 Gene Editing Animal Model Generation	VCAM-1 gene conventional knockout animals VCAM-1 gene conditional knockout animals VCAM-1 point mutation animals VCAM-1 knockin animals	Mouse, rat, rabbit, zebrafish, C. elegans, etc.

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