JAM-B

Detailed Information

Recent Research

The junctional adhesion molecule B (JAM-B) is a multifunctional transmembrane protein, which belongs to the immunoglobulin superfamily (IgSF). JAM-B is located at cell contact and is enriched at the junction of epithelial and endothelial cells, as well as on the surface of erythrocytes, leukocytes, and platelets. It has shown that JAM-B plays an important role in numerous cellular processes, such as tight junction assembly, regulation of paracellular permeability, spermatogenesis, angiogenesis,leukocytic transmigration, tumour metastasis and cell proliferation. Some reports showed that blocking the interactions of JAM-B and -C can reduce monocyte numbers in the ablumenal compartment by increasing reverse transmigration rather than through reducing transmigration.

JAM-B and Malignancy

Tumor metastasis is the movement or spreading of tumor cells from the primary site to a distant one. Circulating tumor cells isolated from primary tumors may interact with vascular endothelial cells during blood metastasis. Metastatic and invasive potential of a tumor cell depends on the expression of various proteins at each step of the metastatic cascade. Several reports showed that JAM-B played an important role in the metastasis of tumor cells.

JAM-B and gastric carcinoma

Gastric cancer, one of the most common malignancies, is the second leading cause of cancer-related death globally. Deregulation of the expression and function of TJ proteins leads to the occurrence and development of cancer by activation of cytoskeleton mechanism.Some reports have shown that JAM-B was levels in tumor samples were significantly up-regulated compared to adjacent normal tissues, and that JAM-B levels were higher in higher-grade tumors than in lower-grade and medium-grade ones. Moreover, JAM-B and JAM-C activated the expression of actin filament-associated protein (AFAP) gene,the expression of AFAP was significantly increased as a downstream factor of JAM-B and JAM-C. Recently, one report has shown that JAM-B was only expressed in primary tumors. Overall, deregulation of JAM-B and JAM-C expression may potentially be involved in progression of gastric adenocarcinoma tumors.

JAM-B and colorectal cancer

One report showed that JAM-B was expressed at very low levels in colorectal cancer due to JAM-B genes being hypermethylatedon promoters in CpG islands. Besides, it is reported that JAM-B was expressed at lower levels in adenocarcinoma and adenoma than in normal colonic mucosa, and JAM-B has the lowest expression levels in adenoma.

JAM-B and glioma

Brain invasion is a biological hallmark of glioma which contributes to its aggressiveness and prognosis.Deregulated expression of JAMs in glioma cells has been implicated in this process. Recently, a study showed that JAM-B was aberrantly expressed in glioma as a high affinity JAM-C ligand. The interaction of JAM-B and JAM-C could activate c-Src proto-oncogene, which is known as a central upstream molecule in the pathways regulating cell invasion and migration. Also it was shown that JAM-B/C blocking antibodies impaired in vivo glioma invasion and proliferation in mice.

JAM-B and melanoma

Melanoma is the most dangerous type of skin cancer. Many factors have been proposed to influence the metastasis of melanoma in patients. Some reports indicated that JAM-B expressed by endothelial cells was involved in melanoma cell metastasis via its interaction with JAM-C on tumor cells. Furthermore, using a JAM-B-deficient mouse model, it was found that the differential migration disappeared between JAM-C expressing cells and JAM-C silenced cells, revealing that JAM-B acted as a counter-receptor for JAM-C mediated reservation of melanoma cells in the lungs.

JAM-B and esophageal squamous cell carcinoma (ESCC)

Esophageal squamous cell carcinoma is an aggressive and malignant tumor for which there is limited treatment option. The reason for this is that most cases are diagnosed late, and patients are already in the advanced stages of the disease. Lymph node metastasis often arises from this type of cancer due to the rich lymphatic drainage system in the esophagus. Recently, it was demonstrated that the methylation of JAM-B was increased in the region downstream of the gene and its expression was decreased. Furthermore, some reports showed that the expression JAM-B was down-regulated and JAM-B was identified as a key player in the signal transduction networks in ESCC.

JAM-B and breast cancer

In females, breast cancer is the leading cancer with high incidence and frequently diagnosed malignancy, with lower survival rates in patients. JAM-B is a necessary component of apical junctional components. One report showed that JAM-B was associated with breast cancer progression. JAM-B had a significantly lower level in breast tumors from patients who developed metastasis than those who were disease-free. It means that JAM-B decreased migration and metastasis of breast cancer cells. In contrast, JAM-A expression was up-regulated in breast cancer tissues compared to the normal specimen and was correlated to reduced survival of breast tumor patients.

JAM-B and lung cancer

Lung cancer is a malignant lung tumor characterized by uncontrolled cell proliferation in tissues of the lung. One report showed that over-expression of JAM-B in a trisomy-21 mouse model of Down's syndrome was responsible for inhibiting VEGF-induced angiogenesis and, thus, restraining tumor effects in a lung carcinoma mouse model. Conversely, the expression level of JAM-A in lung tumor tissues was higher than corresponding normal lung tissues and served as a negative predictor of survival in lung cancer patients.

JAM-B and oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) characteristically metastasizes from the primary organ to regional lymph nodes in the early stages of the cancer. It was demonstrated that JAM-B correlated with the metastatic potential, as it was up-regulated in human oral cancer LNM Tca8113 cells which metastasized to lymph nodes at a higher rate than its parental cell line Tca8113. Therefore it was suggested JAM-B acts as a potential factor for the metastasis of OSCC.

JAM-B and other diseases

A study on inflammation indicated JAM-B expression was restricted to the endothelium of arterioles in and adjacent to lymphocytic inflammation sites but was not discovered in liver specimens, signifying JAM-B may only be inducible in some inflammatory tissue types. Another similar study showed that JAM-B was involved in leukocyte extravasation to inflammation sites. Moreover, it was reported that JAM-B interfered with angiogenic VEGF/VEGFR2 signaling which is a major pathway necessary for tumor angiogenesis, suggesting JAM-B could provide a useful possibility for the diagnosis and treatment of relevant diseases.

Conclusion

JAM-B interacts with various receptors and cytokines to modulate downstream signal transduction. It has been shown that JAM-B is an important regulator in various diseases. Thus, JAM-B may have different potentiality in the regulation of cancer metastasis. In the future JAM-B may well provide preoperative diagnosis and a new avenue for targeted therapy in certain malignancies.