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ADAM28

Official Full Name
ADAM metallopeptidase domain 28
Background
This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene is a lymphocyte-expressed ADAM protein. Alternative splicing results in two transcript variants. The shorter version encodes a secreted isoform, while the longer version encodes a transmembrane isoform. [provided by RefSeq, Jul 2008]
Synonyms
ADAM28; ADAM metallopeptidase domain 28; MDCL; MDC-L; ADAM23; MDC-Lm; MDC-Ls; eMDCII; ADAM 28; eMDC II; disintegrin and metalloproteinase domain-containing protein 28; metalloproteinase-like, disintegrin-like, and cysteine-rich protein-L; epididymal metalloproteinase-like, disintegrin-like, and cysteine-rich protein II; epididymial metalloproteinase-like, disintegrin-like, and cysteine-rich protein II; zgc:153755; si:ch211-133n22.1; a disintegrin and metallopeptidase domain 28

Cat.No. Product Name Price
AD00643ZHuman ADAM28 adenoviral particlesInquiry

A disintegrin and metalloproteinase 28 (ADAM28) is a member of the ADAM family. In the protein sequence, it is closer to snake venom metalloproteinases (SVMPs) than other members, so it can cut a similar substrate for snake venom metalloproteinases. ADAM28 has two isomorphs: membrane anchoring (ADAM28m) and secretory (ADAM28s). In human tissues, ADAM28m is expressed on the surface of the spleen, lymph nodes and T, B lymphocytes and peripheral blood lymphocytes; ADAM28s is mainly expressed in the spleen. Recent studies have shown that human ADAM28 is expressed in odontogenic cells. ADAM28 has the functions of cell adhesion and proteolytic enzymes and plays an important role in cell activities such as degradation of extracellular matrix, cell-cell adhesion, cell-matrix adhesion, cell fusion and signal transduction. ADAM28 is involved in the pathological processes of multiple solid tumor formations, invasion, and metastasis in vivo, so its targeted therapy in tumors may have important clinical significance.

The molecular mechanism of ADAM28 gene expression in cancer cells remains elusive. Abe et al. found that ADAM28 is expressed in Madin-Darby canine kidney epithelial cells transformed with oncogenes, including v-src, LMP1, ErbB2, Ha-Ras and c-Fos. The v-src transformants were found to selectively induce ADAM28. Implantation of v-src transformants showed progressive tumors that were significantly inhibited by local injection of anti-ADAM28 antibodies. By treatment with Src kinase, mitogen-activated protein kinase kinase (MEK), phosphatidylinositol 3-kinase (PI3K) or mammalian target rapamycin, radicicol, or a mixture of MEK and PI3K inhibitors, the expression of ADAM28 in the v-sc transformants was partially inhibited and eliminated by the v-Src kinase inhibitor. Human cancer cell lines of the lung, breast, ovary, kidney, and colon show ADAM28 expression, which is associated with phosphorylation of c-Src and is inhibited by inhibitors in a similar manner to v-src transformants.

ADAM28 Figure 1. Schematic presentation of the Src effector pathways that may be involved in Src-induced expression of ADAM28. (Abe, H., et al. 2013)

ADAM28 and Leukemia

Human membrane-anchored ADAM28m is expressed on the surface of human peripheral blood lymphocytes. Studies by Bret et al have shown that ADAM28 is overexpressed in normal memory B cells. Another report suggests that ADAM28 is highly expressed in B lymphocyte profiles in humans and mice, especially chronic B lymphoblastic leukemia.

CD200 is a type I membrane glycoprotein that is a highly conserved member of the immunoglobulin superfamily. It can be expressed in a variety of human cells including B cells and activated T cells. CD200 can exert immunomodulatory effects by binding to receptors on the surface of myeloid cells to affect cell function. CD200 is elevated in a variety of hematological malignancies and is associated with progression and prognosis of lymphoma and leukemia. In chronic lymphocytic leukemia, the expression level of soluble CD200 (sCD200) is positively correlated with the expression level of ADAM28 mRNA in CD5 + cells. When ADAM28 expression was inhibited by small interfering RNA (siRNA), the amount of sCD200 released from tumor cells was significantly reduced. This result is consistent with the hypothesis that ADAM28 mediates CD200 shedding on the cell surface. Further, it was found that secreted ADAM28s expressed more in the spleen and lymph nodes, but their mRNA expression levels were not associated with sCD200. Therefore, it is hypothesized that secreted ADAM28s and membrane-anchored ADAM28m play different roles in tumor progression. ADAM28s are not involved in the core process of sCD200 shedding, and ADAM28m is the primary factor in this biological process.

ADAM28 and Non-small Cell Lung Cancer

In vitro studies have found that human lung cancer cells (PC-9 and Calu-3) are the higher expression of ADAM28 than breast cancer cells (MDA-MB231 and MCF-7), renal cell carcinoma cells (CAKI-2 and 769P), and liver cancer cells (HepG2). Zucker et al. found that the expression level of ADAM28 is associated with rapid growth and metastatic tumors such as human lung cancer. Membrane-anchored ADAM28m and secreted ADAM28s are associated with lung tumor metastasis. Clinical studies such as Lv et al. have shown that the expression of ADAM28 non-small cell lung cancer is significantly increased in advanced patients, and the expression level is related to clinical tumor size, tumor cell proliferation status and lymph node metastasis. Serum ADAM28 levels can be used as biomarkers for the chemotherapy effect of lung cancer. The baseline expression level of ADAM28 and the upper bound of ADAM28 are independent survival predictors for patients with advanced lung cancer.

ADAM28 and Other Cancers

Clinical studies have found that ADAM28 levels are positively correlated with tumor size in patients with lung adenocarcinomas with a tumor diameter of no more than 20 mm. The results of immunostaining showed that the survival rate of ADAM28 immunoreactive lung adenocarcinoma patients was lower than that of the control group. Studies have shown that serum and tumor cell surface ADAM28 is highly expressed and can be a biomarker for non-small cell lung cancer. Studies have shown that asbestos-related lung cancer and the control group have found that ADAM28 is significantly increased in patients with lung cancer induced by asbestos. ADAM28 is also considered to be one of the biomarkers of lung tumors caused by asbestos.

In the distribution of anatomical locations of head and neck squamous cell carcinoma, ADAM28 is more likely to be highly expressed in pharyngeal tumor cells; in the histopathological staging of tumors, ADAM28 is the most highly expressed in stage II tumors (medium differentiated tumors). ADAM28 detected in tissues of patients with overweight or obese colorectal cancer or in prostate cancer cell lines may be predictive of tumor metastasis. In addition, studies have found that ADAM28 can be used as an effective diagnostic marker for distinguishing between low-grade malignant chondrosarcoma and endogenous chondromatosis. The study also found that the expression of ADAM28 in chondroblastoma was higher than that of conventional chondrosarcoma.

References:

  1. Abe, H., Mochizuki, S., Ohara, K., Ueno, M., Ochiai, H., & Kitagawa, Y., et al. (2013). Src plays a key role in adam28 expression in v- src –transformed epithelial cells and human carcinoma cells. American Journal of Pathology, 183(5), 1667-1678.
  2. Twito, T., Chen, Z., Khatri, I., Wong, K., Spaner, D., & Gorczynski, R. (2013). Ectodomain shedding of cd200 from the b-cll cell surface is regulated by adam28 expression. Leukemia Research, 37(7), 816-821.
  3. Nowakowskazajdel, E., Mazurek, U., Wierzgon, J., Kokot, T., Fatyga, E., & Ziolko, E., et al. (2013). Expression of adam28 and igfbp-3 genes in patients with colorectal cancer - a preliminary report. Int J Immunopathol Pharmacol, 26(1), 223-228.
  4. Zhang, X. H., Wang, C. C., Jiang, Q., Yang, S. M., Jiang, H., & Lu, J., et al. (2015). Adam28 overexpression regulated via the pi3k/akt pathway is associated with relapse in de novo, adult b-cell acute lymphoblastic leukemia. Leukemia Research, 39(11), 1229-1238.
  5. Zhu XL, Wang QM, Feng FE, Zheng XL, & Zhang XH. (2014). research advances on adam28 expression and adam28-mediated tumor metastasis. Journal of Experimental Hematology, 22(4), 1142-1147.

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