Expression of the Metastasis Suppressor KAI1 in Decidual Cells at the Human Maternal-Fetal Interface

Abstract

At the human maternal-fetal interface, the decidua forms a dense matrix that is believed to limit trophoblast invasion. We investigated whether the metastasis suppressor KAI1 (CD82) is expressed at the maternal-fetal interface. Immunohistochemistry showed strong expression of KAI1 in decidual cells, whereas trophoblast cells were negative for KAI1. In luteal phase endometrium, KAI1 was present in decidualizing endometrial stromal cells. We investigated whether KAI1 expression in endometrial stromal cells is regulated by the decidualizing stimuli cAMP and progesterone or by the cytokine interleukin ( Successful pregnancy requires coordinate progression of decidualization, placenta formation, and embryo development. Decidualization is a differentiation process of the endometrium, the mucosa lining the uterine lumen. In humans, decidualization occurs independently of the presence of a conceptus during the second half of the menstrual cycle and is controlled by progesterone-and cAMP-dependent events and modulated by cytokines, such as interleukin-1␤ (IL-1␤), in a complex crosstalk of endocrine, paracrine, and autocrine signals.

CD82 gene suppression in endometrial stromal cells leads to increase of the cell invasiveness in the endometriotic milieu

“…The growing evidence shows that CD82 inhibits cell motility through regulating the associated protein such as integrin (Mannion et al 1996, Sugiura & Berditchevski 1999, Sridhar & Miranti 2006, epidermal growth factor receptor (EGFR; Odintsova et al 2000), and Duffy antigen receptor for chemokines (DARC; Bandyopadhyay et al 2006). The expression of CD82 is involved in decidual transformation from human endometrial stromal cells (ESCs; Gellersen et al 2007). Moreover, our previous work has confirmed that CD82 in decidual stromal cells controls the trophoblasts invasiveness by suppressing integrinb1/mitogen-activated protein kinase (MAPK)/ ERK1/2 signal pathway in human early pregnancy (Li et al 2010).…”

Mechanisms of KAI1/CD82-Induced Prostate Cancer Metastasis

“…recently shown to positively control the expression of a protein in decidual cells involved in limiting trophoblast invasion at the maternal-fetal interface [33]. In metastatic cells KiSS binds its receptor on fibroblasts rather than the tumor cells to indirectly suppress tumor cell growth at the site of colonization [219].…”

“…The mouse promoter contains many of the same putative promoter elements [19]. Several extracellular stimuli have been reported to enhance CD82 expression and include cytokines (IL-1β, IL-4, IL-6, IL-13, IFN-γ, TNF-α), growth factors (NGF), phorbol esters (PMA), drugs (Genistein, etoposide), and 8-bromo-cAMP [11,[33][34][35][36][37][38][39]. The mechanisms by which these stimuli regulate CD82 transcription are virtually unknown, except that NF-κB is known to mediate some of the effects of the cytokines.…”

Tetraspanin KAI1/CD82 inhibits cell migration-related cellular events via reorganizing actin network

“…This interaction can trigger the senescene of cancer cell and completely abolish the lung metastasis of rat prostatic carcinoma cell line AT6.1, the human breast carcinoma cell line MDA-MB-435, and the mouse melanoma cell lines B16BL6 and B16F10 (Bandyopadhyay et al, 2006;Zijlstra and Quigley, 2006;Gellersen et al, 2007;Iiizumi et al, 2007). However, in DARC knockout mice, this inhibition of metastasis has been significantly impaired.…”

“…It has been reported that at least three genes are involved in this process. They are Nm23 ( Fournier et al, 2002;Hartsough et al, 2002;Palacios et al, 2002;D'Angelo et al, 2004;Engel et al, 2004), medroxyprogesterone (MPA) (Ouatas et al, 2003;Palmieri et al, 2005), and KAI1 (Bandyopadhyay et al, 2006;Zijlstra and Quigley, 2006;Gellersen et al, 2007;Iiizumi et al, 2007). Here, Iwill focus on how KAI1/CD82 inhibits cancer cell metastasis.…”