The tetraspanin CD82 is a potent suppressor of tumor metastasis and regulates several processes including signal transduction, cell adhesion, motility, and aggregation.
SIGNIFICANCE STATEMENT: The cell-surface and ER transmembrane protein gp78/AMFR, a receptor for the prometastatic autocrine motility factor (AMF), as well as an E3 ubiquitin-ligase involved in the ER-associated degradation (ERAD) of not only the tumor metastatic suppressor KAI1 but also of hepatic cytochromes P450, is upregulated in various human cancers, enhancing their invasiveness, metastatic potential, and poor prognosis.
Vasculogenic mimicry (VM, new blood supply formation in malignant tumors), E-Cadherin (a calcium-dependent transmembrane glycoprotein that mediates intercellular adhesion), KAI1 (a suppressor gene of tumor metastasis) are all valuable factors for metastasis and prognosis in diverse common human cancers.
In RA-synovium, CD82 was expressed in RASF close to blood vessels, LL, sites of cartilage invasion and colocalised with distinct integrins involved in tumour metastasis suppression but also in RA-synovium by RASF.
In multivariate analysis, high VM, Notch4, DLL4 levels, tumor size, LNM, DM, TNM stage, and low KAI1/CD82 levels were potential to be independent prognostic factors for overall survival time (OST) in NSCLC patients.VM and the expression of Notch4, DLL4, and KAI1/CD82 represent promising markers for tumor metastasis and prognosis, and maybe potential therapeutic targets for NSCLC.
In this review, we focus on the differential expression of KAI1/CD82, a tumor metastasis suppressor gene that can inhibit cancer invasion and cell metastasis during NSCLC.
Vasculogenic mimicry (VM, blood supply formation often seen in highly aggressive tumors), Aldehyde dehydrogenase 1 (ALDH1, a biomarker of cancer stem cells), KAI1 (a suppressor gene of tumor metastasis) are all valuable factors for metastasis and prognosis in diverse human cancers.
The present study aimed to investigate the expression of cluster of differentiation 82 (KAI1), a gene involved in the suppression of tumor metastasis, in human retinoblastoma (RB) tissue and to study the effect of KAI1 expression on RB cell migration and invasion.
Subsequent investigations revealed that Cx32 directly enhanced the acetylation and transcriptional activity of p53, thus upregulating the expression of the tumor metastasis suppressor protein KAI1/CD82, which is a p53 target gene.
KAI1/CD82 has been reported to attenuate the process of metastases in a variety of tumors; however, its mechanism of action in invasion has not been fully elucidated.
Analyses of metastases with and without KAI1 transfection in mice were different in liver and lung between controls 1.62 +/- 0.39, 0.45 +/- 0.09, pCMV-KAI 1.01 +/- 0.27, 0.33 +/- 0.09 and KAI1-Lipofectamine 0.99 +/- 0.21, 0.30 +/- 0.09 respectively (P < 0.05).
In both cases, we found that the delivery of either MRP-1/CD9 or KAI1/CD82 cDNA dramatically reduced the metastases to the mediastinal lymph nodes in comparison with those of LacZ gene delivery, without affecting the primary tumor growth at the implanted site.
Downregulation of KAI1 has been found to be clinically associated with metastatic progression in a variety of cancers, whereas overexpression of CD82 specifically suppresses tumor metastasis in various animal models.
Recently, we have reported the dynamic role of a beta-catenin-reptin chromatin remodelling complex in regulating a metastasis suppressor gene KAI1 (ref.1), which is capable of inhibiting the progression of tumour metastasis.
The expression of CD82 and CD63 was analysed by reverse transcriptase-PCR (RT-PCR) and immunohistochemistry in benign goiter (n=12) and 75 primary thyroid carcinoma tissue specimens (PTC: 33, FTC: 24, UTC: 18) out of which 36 were non-metastasized primary tumors and 39 were metastasized tumors (regional lymph node and/or distant metastases).
KAI1 COOH-terminal interacting tetraspanin (KITENIN), a member of the tetraspanin family, interacts with KAI1, a tumor metastasis suppressor, and enhances metastasis of cancer.