Interaction of duffy antigen receptor for chemokines and KAI1 : A critical step in metastasis suppression

Tumor metastases suppressor protein KAI1/CD82 is capable of blocking the tumor metastases without affecting the primary tumor formation, and its expression is significantly down-regulated in many types of human cancers. However, the exact molecular mechanism of the suppressor function of KAI1 remain...

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Published inCancer research (Chicago, Ill.) Vol. 67; no. 4; pp. 1411 - 1414
Main Authors IIIZUMI, Megumi, BANDYOPADHYAY, Sucharita, WATABE, Kounosuke
Format Journal Article
LanguageEnglish
Published Philadelphia, PA American Association for Cancer Research 15.02.2007
Subjects
Antineoplastic agents
Biological and medical sciences
Duffy Blood-Group System - metabolism
Endothelial Cells - metabolism
Humans
Kangai-1 Protein - metabolism
Medical sciences
Neoplasm Metastasis
Neoplasms - metabolism
Neoplasms - pathology
Pharmacology. Drug treatments
Receptors, Cell Surface - metabolism
Tumors
Antigen
Blood group
Metastasis suppressor gene
Interaction
Duffy system
Chemokine receptor
Malignant tumor
Metastasis
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Summary:Tumor metastases suppressor protein KAI1/CD82 is capable of blocking the tumor metastases without affecting the primary tumor formation, and its expression is significantly down-regulated in many types of human cancers. However, the exact molecular mechanism of the suppressor function of KAI1 remains elusive. Evidence from our laboratory supports a model in which tumor cells dislodge from the primary tumor and intravasate into the blood or lymphatic vessels followed by attachment to the endothelial cell surface whereby KAI1 interacts with the Duffy antigen receptor for chemokines (DARC) protein. This interaction transmits a senescent signal to cancer cells expressing KAI1, whereas cells that lost KAI1 expression can proliferate, potentially giving rise to metastases. Our model of the mechanism of action of KAI1 shows that metastasis suppressor activity can be dependent on interaction with host tissue and explains how KAI1 suppresses metastasis without affecting primary tumor formation. Taken together, in vitro and in vivo studies identify the KAI1-DARC interaction as a potential target for cancer therapy.
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ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-06-3801