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PubMed1995

Assembly and function of integrin receptors is dependent on opposing alpha and beta cytoplasmic domains.

The membrane proximal regions of integrin alpha and beta subunits are highly conserved in evolution. In particular, all integrin alpha subunits share the KXGFFKR sequence at the beginning of their cytoplasmic domains. Previous work has shown that this domain is important in integrin receptor assembly. Using chimeric integrin alpha and beta subunits, we show that the native cytoplasmic domains of both subunits must be present for efficient assembly. Most strikingly, chimeric alpha 1 and beta 1 subunits with reciprocally swapped intracellular domains dimerize selectively into collagen IV receptors expressed at high levels on the surface. However, these receptors, which bind ligand efficiently, are deficient in a variety of post-ligand binding events, including cytoskeletal association and induction of tyrosine phosphorylation. Furthermore, deletion of the distal alpha cytoplasmic domain in the swapped heterodimers leads to ligand-independent focal contact localization, which also occurs in wild-type subunits when the distal cytoplasmic domain is deleted. These results show that proper integrin assembly requires opposed alpha and beta cytoplasmic domains, and this opposition prevents ligand-independent focal contact localization. Our working hypothesis is that these two domains may associate during receptor assembly and provide the mechanism for integrin receptor latency.

3T3 Cells↗
PubMed1996

The membrane-cytoplasm interface of integrin alpha subunits is critical for receptor latency.

Localization of integrin receptors to focal contact sites occurs upon ligand binding. This activity is latent, since unoccupied integrin receptors do not localize to focal contacts. Deletion analysis has revealed that the alpha cytoplasmic domains is required for the maintenance of integrin receptor latency. Our current hypothesis for the mechanism of integrin post-ligand binding events is that there is a change in relationship of alpha and beta cytoplasmic domains, which overcomes receptor latency. One possible mechanism for such a change would involve the amino acid residues at the membrane-cytoplasm interface. To test this hypothesis, we have produced point mutations in the human integrin alpha 1 subunit. These mutations had no effect on the adhesion via alpha 1 beta 1 to its ligand, collagen IV. However, receptor latency is lost in one of these mutants, leading to constitutive focal contact localization. This effect did not occur in receptors with an exchange of intracellular domains, suggesting that the mechanism of loss of latency involves a relative motion of the integrin chains. These results suggest a model in which post-ligand binding events in integrin receptors are associated with changes in the position of the alpha and beta cytoplasmic domains.

3T3 Cells↗
PubMed2006

The effects of oxygen concentration and gestational age on extravillous trophoblast outgrowth in a human first trimester villous explant model.

BACKGROUND: In the first trimester of human pregnancy, extravillous trophoblasts from placental villi invade the decidua temporarily occluding the spiral arteries, preventing maternal blood flow and creating a low-oxygen environment, which is believed to play an important role in the regulation of extravillous trophoblast outgrowth. This work aimed to quantify the effects of gestational age and oxygen concentration on extravillous trophoblast outgrowth. METHODS: A quantitative first trimester villous explant model was used to measure the frequency and area of extravillous trophoblast outgrowths from villi grown in 1.5 or 8% oxygen. RESULTS: The percentage of explants producing outgrowth declined independently of oxygen concentration as gestation increased from 8 to 12 weeks. Culture in 1.5% oxygen significantly reduced the frequency and area of outgrowths in comparison with 8% oxygen. HLA-G and alpha1 integrin were both expressed throughout outgrowths, with no difference in the expression between oxygen concentrations. Gestation influenced the response of explants to oxygen, with a significant differential response to oxygen concentration in placentae under 11 weeks of gestation, whereas in villi from placentae of 11 or 12 weeks, no differential response was observed. CONCLUSIONS: In the first trimester, oxygen and gestational age both regulate extravillous trophoblast outgrowth.

Abortion, Induced↗
PubMed1995

Involvement of alpha 1 and alpha 4 integrins in gut mucosal injury of graft-versus-host disease.

We have investigated the involvement of adhesion molecules in the lymphocyte infiltration associated with acute intestinal graft-versus-host disease (GVHD) induced by injection of C3H lymph node cells into irradiated (C3H x DBA/2)F1 mice. First we analyzed the expression profile of adhesion molecules including alpha 1, alpha 2, alpha 4, alpha 5, alpha 6, alpha L and beta 7 integrins, CD44 and L-selectin of lymphocytes from lymph nodes and gut mucosa in normal mice. In normal mice, intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) uniquely showed increased expression of alpha 1, alpha 2 and beta 7 integrins, and decreased expression of L-selectin compared with that of lymphocytes of the lymph nodes and Peyer's patches. In mice with GVHD, IEL and LPL of donor lymph node cells origin underwent phenotypic changes characterized by the increased expression of alpha 1, alpha L and beta 7 integrins, and the loss of L-selectin. The expression profile of adhesion molecules on IEL and LPL of GVHD mice resembled that of normal mice except for the lack of alpha 2 integrin. Treatment of GVHD mice with anti-alpha 1, -alpha 4 or -beta 7 integrin antibody alone partially prevented the mucosal pathology of intestinal GVHD, whereas only mice treated with anti-alpha 1 showed reduced donor lymphocytic infiltration into the intestinal mucosa. In contrast, treatment with anti-alpha L or anti-CD44 antibody did not affect the intestinal GVHD. Furthermore, dual blockade of both alpha 1 and alpha 4 integrins completely inhibited the mucosal pathology and donor lymphocyte infiltration of intestinal GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Integrin expression in cells of the intervertebral disc.

In this study, we investigated the profile of integrin expression in human and porcine intervertebral disc tissue. Differences in extracellular matrix composition between anulus fibrosus (AF) and nucleus pulposus (NP) regions of the disc, as well as differences in cellular responses to environmental stimuli, suggest a role for integrins in presenting matrix signals that may mediate these responses. Human disc tissue and porcine AF and NP tissue were stained with antibodies to alpha integrin subunits 1-6, V and IIb, and beta integrin subunits 1-6 and graded for evidence of positive staining on a scale from 0 (no staining) to 3 (high incidence of staining). Human tissue expressed alpha and beta integrin subunits shown to be present in articular cartilage, including alpha(1), alpha(5) and alpha(V). Porcine AF tissue expressed similar integrin subunits to human disc, with both expressing alpha(1), alpha(5), beta(1), beta(3) and beta(5) subunits, whereas porcine NP tissue expressed higher levels of alpha(6), beta(1) and beta(4) than AF tissue. The expressed subunits are known to interact with proteins including collagens, fibronectin and laminin; however, additional studies will be required to characterize the interactions of the integrin subunits with specific matrix constituents, as well as their specific involvement in regulating environmental stimuli.

Animals↗
PubMed1996

A functional monoclonal antibody recognizing the human alpha 1-integrin I-domain.

Alpha 1 beta 1 heterodimer is a member of the integrin receptor superfamily that has been described to be involved in cell-matrix binding through its interaction with collagens, fibronectin and laminin. The alpha 1 integrin belongs to a subset of I-domain containing integrins that includes alpha M, alpha L, alpha X and alpha 2. In this study we describe an anti-alpha 1 mAb (FB12) that recognizes an epitope located in the human alpha 1 I-domain, since the mAb can bind to human, but not to rat, recombinant I-domain GST fusion protein. FB12 mAb efficiently and specifically inhibits the binding of activated human lymphocytes to laminin, collagen and fibronectin. These data support the notion that the alpha 1 I-domain itself has an important role in receptor-ligand binding. In particular, we show that alpha 1 integrin-dependent lymphocyte adhesion to fibronectin is I-domain mediated, at variance with the RGD-dependent adhesion which seems to be mediated by the beta 1 rather than the alpha 1 integrin chain. Lastly, the overexpression of the alpha 1-integrin by stromal cells and blood vessels of solid tumors may suggest a role for this integrin in tumor biology.

Animals↗
PubMed1999

Involvement of host cell tyrosine phosphorylation in the invasion of HEp-2 cells by Bartonella bacilliformis.

We have provided evidence that exposure of human cells to protein kinase inhibitors results in decreased invasion of these cells by Bartonella bacilliformis in a dose-dependent manner. Preincubation of human laryngeal epithelial cells in the presence of genistein, a tyrosine protein kinase inhibitor, decreased the invasion of these cells by B. bacilliformis significantly. Further, exposure of normal human umbilical vein endothelial cells to staurosporine, a potent inhibitor of protein kinase C and some tyrosine protein kinases, resulted in a considerable reduction in the number of organisms internalized by these cells. Moreover, Bartonella infection of HEp-2 cells induced tyrosine phosphorylation of several Triton X-100 soluble proteins with approximate molecular masses of 243, 215 179, 172 (doublet), 160, 145 and 110 kDa that were absent or reduced in the presence of genistein in cells after 1 h of infection. Exposure of HEp-2 cell monolayers to anti-alpha 5 and anti-beta 1 chain integrin monoclonal antibodies resulted in a moderate decrease in the invasion of these cells, suggesting a possible role of alpha 5 beta 1 integrins in the uptake of Bartonella into nucleated cells.

Antibodies, Monoclonal↗
PubMed2006

Oxidative stress-responsive transcription factor ATF3 potentially mediates diabetic angiopathy.

Previous results of our cDNA microarray analysis to look for genes whose expression level correlates well with in vitro tubulogenesis by NP31 endothelial cells revealed the transcription factor ATF3 known to be responsive to stress such as reactive oxygen species (ROS). Anti-ATF3 small interfering RNA gave an inhibitory influence on tube formation by NP31 cells expressing an activated form of the vascular endothelial growth factor receptor 1 (VEGFR-1) kinase. When expression of ATF3 was regulated under the control of tetracycline system in NP31 cells, they acquired the tubulogenic ability upon ATF3 induction. While ATF3 failed to induce expressions of VEGF and VEGFR, it regulated those of CDK2, CDK4, p8, plasminogen activator inhibitor 1, integrin alpha1, subunit and matrix metalloprotease MMP13. In H2O2-stimulated NP31 cells as well as endothelial cells of glomerulus and aorta of Otsuka-Long-Evans-Tokushima-Fatty diabetic model rats, concomitantly enhanced expressions of ATF3, PAI-1, and p8 were observed. Given the proposed hypothesis of the close linkage between diabetic angiopathy and ROS, those data suggest that ROS-associated diabetic complication may involve ATF3-mediated pathological angiogenesis.

Activating Transcription Factor 3↗
PubMed2006

Stem cell-derived Sca-1+ progenitors differentiate into smooth muscle cells, which is mediated by collagen IV-integrin alpha1/beta1/alphav and PDGF receptor pathways.

Embryonic stem (ES) cells can differentiate into smooth muscle cells (SMCs) that can be used for tissue engineering and repair of damaged organs. However, little is known about the molecular mechanisms of differentiation in these cells. In the present study, we found collagen IV can promote ES cells to differentiate into stem cell antigen-1-positive (Sca-1(+)) progenitor cells and SMCs. Pretreatment of ES cells with antibodies against collagen IV significantly inhibited SMC marker expression. To further elucidate the effect of collagen IV on the induction and maintenance of SMC differentiation, Sca-1(+) progenitor cells were isolated with magnetic beads, placed in collagen-IV-coated flasks, and cultured in differentiation medium with or without platelet-derived growth factor (PDGF)-BB for 6-90 days. Both immunostaining and fluorescence-activated cell sorter analyses revealed that the majority of these cells were positive for SMC-specific markers. Pretreatment of Sca-1(+) progenitors with antibodies against integrin alpha(1), alpha(v), and beta(1), but not beta(3), inhibited focal adhesion kinase (FAK) and paxillin phosphorylation and resulted in a marked inhibition of SMC differentiation. Various tyrosine kinase inhibitors, and specific siRNA for phosphatidylinositol 3-kinase (PI 3-kinase) and PDGF receptor-beta significantly inhibited SMC marker expression. Taken together, we demonstrate for the first time that collagen IV plays a crucial role in the early stage of SMC differentiation and that integrin (alpha(1), beta(1), and alpha(v))-FAK-PI 3-kinase-mitogen-activated protein kinase and PDGF receptor-beta signaling pathways are involved in SMC differentiation.

Animals↗
PubMed2004

Alpha L-integrin I domain cyclic peptide antagonist selectively inhibits T cell adhesion to pancreatic islet microvascular endothelium.

Insulitis is a hallmark feature of autoimmune diabetes that ultimately results in islet beta-cell destruction. We examined integrin requirements and specific inhibition of integrin structure in T cell and monocyte adhesion to pancreatic islet endothelium. Examination of cell surface integrin expression on WEHI 7.1 T cells revealed prominent expression of beta-, beta(1)-, alpha(L)-integrins, and low expression of alpha(M)-integrins; whereas WEHI 274.1 monocytes showed significant staining for beta(2)-, beta(1)-, alpha(M)-molecules and no expression of alpha(L)-molecules. Unstimulated islet endothelium showed constitutive levels of ICAM-1 counter-ligand expression with minimal VCAM-1 expression; however, TNF-alpha stimulation increased cell surface density of both molecules. TNF-alpha increased T cell and monocyte rolling and adhesion under hydrodynamic flow conditions. Administration of a cyclic peptide competitor for the alpha(L)-integrin I domain binding sites (cyclo1,12-PenITDGEATDSGC) blocked T cell adhesion without inhibiting monocyte adhesion. Examination of T cell rolling revealed that cLAB.L treatment increased the average rolling velocity on activated endothelium and significantly decreased the fraction of T cells rolling at < or =50 microm/s, suggesting that cLAB.L treatment interferes with signal activation events required for the conversion of T cell rolling to firm adhesion. These data demonstrate for the first time that cyclic peptide antagonists against alpha(L)-integrin I domain attenuate T cell recruitment to islet endothelium.

Animals↗
PubMed2003

Negative impact of DEP exposure on human airway epithelial cell adhesion, stiffness, and repair.

Epidemiological and experimental studies suggest that diesel exhaust particles (DEPs) may be associated with increased respiratory mortality and morbidity. Several recent studies have also shown that DEPs increase the production of inflammatory cytokines by human bronchial epithelium (HBE) cells in vitro. The present study investigates the effects of DEPs on the interaction of l-HBE cells (16HBE14o-) with the cell and matrix microenvironment based on evaluation of integrin-type cell/matrix ligand expression, cytoskeleton (CSK) stiffness, and matrix remodeling via matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9 expression. The results showed that DEP exposure induced: 1) a net dose-dependent decrease in CSK stiffness through actin fibers, 2) a concomitant specific reduction of both alpha(3)- and beta(1)-integrin subunits extensively expressed on the HBE cell surface, 3) a decrease in the level of CD44, which is a major HBE cell-cell and HBE cell-matrix adhesion molecule; and 4) an isolated decrease in MMP-1 expression without any change in tissue inhibitor of matrix metalloproteinase (TIMP)-1 or TIMP-2 tissue inhibitors. Restrictive modulation of cell-matrix interaction, cell-cell connection, CSK stiffness, and fibrillary collagen remodeling results in a decreased wound closure capacity and an increased deadhesion capacity. In conclusion, on the basis of these results, we can propose that, in addition to their ability to increase the production of inflammatory cytokines, DEPs could also alter the links between actin CSK and the extracellular matrix, suggesting that they might facilitate HBE cell detachment in vivo.

Actins↗
PubMed2006

Mesenchymal progenitor cells communicate via alpha and beta integrins with a three-dimensional collagen type I matrix.

BACKGROUND/AIMS: The aim of our study was to investigate interactions of mesenchymal progenitor cells (MPCs) with collagen matrices. METHODS: Human bone-marrow-derived MPCs were cultivated in collagen type I gels with and without inhibition of beta(1)-integrin by a specific antibody. Collagen gel contraction, cell morphology, expression of integrin subunits and several genes related to matrix synthesis and turnover as well as MPC differentiation were analyzed over 14 days. RESULTS: Human MPCs markedly contracted free-floating collagen gels. Contraction was nearly completely inhibited by blocking beta(1)-integrin. Cellular morphology was elongated in the absence and mostly round in the presence of the antibody. Expression of integrin alpha(1), alpha(2) and beta(1) subunits showed several changes partly dependent on beta(1)-integrin blocking. Expression of matrix metalloproteinase-1 was elevated irrespective of beta(1)-integrin blocking and tenascin-C was subsequently induced during gel contraction. Spontaneous induction of chondrogenic, osteogenic or adipogenic differentiation was observed neither in the presence nor in the absence of the beta(1)-integrin antibody. CONCLUSION: Our results indicate that the interaction of human MPCs with fibrillar collagen type I involves beta(1)- and alpha-integrin subunits and induces changes in gene expression related to extracellular matrix synthesis and turnover but not differentiation to the chondrogenic, osteogenic or adipogenic phenotype.

Antibodies, Monoclonal↗
PubMed1995

Changes in integrin expression during chondrogenesis in vitro: an immunomorphological study.

Integrins are receptors composed of ligand-specific alpha-chains and cell type-specific beta-chains which are involved in cell-cell and cell-matrix interactions. The distribution of alpha 1- and alpha 3-integrins as well as collagen Types I and II, was investigated by immunofluorescence and immunoelectron microscopy during chondrogenesis in organ culture after various culture periods. Mesenchymal cells from limb buds of Day 12 mouse embryos were grown at high density. Within the first 2 days of the culture period, only alpha 1-integrin could be detected. Formation of cartilage-specific matrix on Day 3 was accompanied by the occurrence of alpha 3-integrin. On Day 7, alpha 3 was present only in cartilage nodules, whereas alpha 1 was strongly expressed in the perichondrium and was more or less homogeneously distributed in the surrounding mesenchyme. On Day 14, alpha 1-integrin was again detectable in cartilage. We suggest that the change in collagen formation from Type I to Type II during chondrogenesis is accompanied by a change in integrin expression from alpha 1 to alpha 3. Conversely, dedifferentiation of chondrocytes in aging cartilage is accompanied by the occurrence of collagen Type I and alpha 1-integrin. Therefore, a strict correlation between the collagen type synthesized by the cells and the appropriate receptor presented by the cells is suggested.

Animals↗
PubMed2005

Platelet-derived soluble factors induce human extravillous trophoblast migration and differentiation: platelets are a possible regulator of trophoblast infiltration into maternal spiral arteries.

In early pregnancy, human extravillous trophoblasts (EVTs) invade and remodel maternal arteries. We have previously demonstrated that CCR1 is expressed on perivascular/endovascular trophoblasts and that CCR1 ligands promote EVT migration. In this study, we examined the physiologic roles of platelet-derived chemoattractants on EVT invasion. By immunohistochemistry, maternal platelets were localized among endovascular trophoblasts within the lumen of spiral arteries. Extracellular matrices (ECMs) were also detected among endovascular trophoblasts and platelets, suggesting that the platelets in these arteries were activated by ECMs. In vitro, platelets attached to EVTs isolated from human villous explant cultures and expressed P-selectin on the cell surface. Platelets significantly enhanced migration of EVTs without affecting proliferation of EVTs or secretion of MMP-2 or MMP-9. The invasion-enhancing effect of platelet-derived culture medium on EVTs was neutralized by anti-CCR1 antibody. Heat treatment completely abrogated the invasion-promoting effects of platelet-derived culture medium, but charcoal stripping did not. Platelets also induced endovascular trophoblast-like morphologic changes and integrin alpha1 expression in EVTs during 48-hour culture. These findings suggest that maternal platelets activated in the spiral arteries can regulate trophoblastic vascular infiltration and differentiation by releasing various soluble factors.

Arteries↗
PubMed1996

Expression of beta 1 integrins in human endometrial stromal and decidual cells.

The present study was undertaken to investigate the expression of beta1 integrins in human endometrium and decidua using flow cytometry, immunohistochemistry, and immunoprecipitation. Fluorescence-activated flow cytometry demonstrated the greater expression of the beta 1, alpha 1, alpha 2, and alpha 5 subunits of the beta1 integrin family in cultured stromal cells from the midsecretory phase, than in those of the early proliferative phase. The addition of estradiol (E2) and progesterone (P) to cultured stromal cells in the early proliferative phase increased the expression of beta1 integrins in vitro. The immunohistochemical distribution of beta1 integrins demonstrated predominantly glandular epithelial staining in the proliferative phase, and mesenchymal and glandular staining in the midsecretory phase. Flow cytometry also demonstrated the expression of the beta 1, alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6 subunits of beta 1 integrin family in cultured decidual cells, and the enriched-fraction of prolactin (PRL)-producing decidual cells isolated by Percoll gradients showed high levels of beta 1, integrins expression. Immunohistochemistry confirmed the beta 1 integrin cell surface phenotypes in cultured decidual cells observed by flow cytometry. Autoradiography of immunoprecipitate subjects to SDS-PAGE revealed three major polypeptides with molecular weights of 130 kDa (beta 1 subunit), 165 kDa (alpha 2 subunit), and 210 kDa (alpha 1 subunit) under reducing conditions. In summary, the present study demonstrated that endometrial stromal and decidual cells expressed beta1 integrin subunits at their surfaces. The expression exhibited a variability throughout the menstrual cycles, being predominantly detected in the secretory phase, and was maintained highly in the decidua. Thus, beta 1 integrins in human endometrium and decidua may be important in mediating the organization of extracellular matrix proteins derived from embryos during the early stage of implantation.

Abortion, Therapeutic↗
PubMed1997

Embryonic regulation of integrins beta 3, alpha 4, and alpha 1 in human endometrial epithelial cells in vitro.

In the present study, we examined the embryonic regulation of beta 3 integrin in human endometrial epithelial cells (EEC) at the protein level and analyzed putative embryonic factors responsible for this regulation. The model employed is based on a clinical in vitro fertilization program in which single human embryos were cocultured with EEC until blastocyst stage and then transferred back to the uterus. After embryo transfer, EEC wells were divided according to the embryonic status reached: EEC with embryos that achieved the blastocyst stage, EEC with arrested embryos, and EEC without embryos. Immunostaining for beta 3 was positive in plasma membrane of EEC. Flow cytometry showed a mean percentage of beta 3-stained cells of 24.1 +/- 5.7 in EEC cocultured with embryos that achieved the blastocyst stage (n = 13) vs. 9.5 +/- 1.6 (P < 0.05) in those EEC cultured with arrested embryos (n = 12). Immunostaining for alpha 1 and alpha 4 integrins was negative in EEC monolayers studied, regardless of the presence or absence of embryos, and these findings were confirmed by flow cytometry. The possibility that the embryonic IL-1 system and leukemia inhibitory factor were involved in the endometrial beta 3 up-regulation was investigated by neutralizing experiments demonstrating a significant inhibition of beta 3-stained cells when EEC monolayers were cultured in the presence of EEC/blastocyst-conditioned media with (n = 4) vs. without (n = 8) antihuman interleukin (IL)-1 alpha + IL-1 beta (1.65% vs. 14.6%; P < 0.05). Dose-response experiments further demonstrated an up-regulation of beta 3 positive cells when IL-1 alpha + IL-1 beta were added to the medium at a concentration of 10 pg/mL compared with control medium without added cytokines (40% vs. 20%, n = 4). The functional relevance of the EEC beta 3 up-regulation was tested using a mouse blastocyst adhesion assay. More mouse blastocysts attached to EEC previously in contact with human blastocyst (72.7%) compared with those EEC previously in contact with arrested embryos (40%). Our results demonstrate the selective effect of a developing human embryo on EEC expression of beta 3, which is maximal when a human blastocyst instead of an arrested embryo is considered. Furthermore, the embryonic IL-1 system seems to be involved in the EEC beta 3 up-regulation, reinforcing the concept of precise paracrine cross-talk between blastocyst and endometrial epithelium during embryonic implantation.

Adult↗
PubMed2003

Expression of integrins and extracellular matrix proteins at the maternal-fetal interface during tubal implantation.

Investigation of the expression pattern of integrins and their extracellular matrix (ECM) ligands in trophoblasts at the maternal-fetal interface during tubal pregnancy may aid better understanding of the adhesion and invasion of acceptable maternal endometrium by trophoblast cells at the very early stage of human gestation. In this study, spatial and temporal alterations of integrins and ECM ligands were examined in specimens of tubal pregnancies during weeks 3-9 of gestation. In situ hybridization and immunohistochemistry revealed that relatively high levels of integrin alpha(1), beta(1), alpha(5) subunits and heterdimer alpha(5)beta(1) as well as ECM ligands, were displayed in trophoblast cells as early as weeks 3-4 of gestation. Expression peaked during weeks 5-7 and then, with the exception of integrin alpha(1), which remained high, declined slightly up to weeks 8-9 of gestation. Immunoreactive fibronectin, laminin and type IV collagen were detected in column cytotrophoblastic cells (CTB) and some invasive extravillous cytotrophoblast (EVCT) cells and the alterations were coincident with those of the corresponding integrin receptors in EVCT cells. Laminin was strongly stained in EVCT cells that had invaded maternal blood vessels and deep into the interstitium. Maternal epithelial, endothelial and stromal cells also expressed these integrins and ECM ligands. The results indicate their involvement in mediating the adhesion of trophoblasts to the epithelium of the maternal Fallopian tube. The upregulated expression of these molecules in column CTB and invasive EVCT cells may also facilitate the invasion of trophoblasts into the maternal interstitium. Moreover, trophoblasts possessed the potential for self-controlled adhesion and invasion and appear to reach peak invasive capability in the second month of tubal implantation.

Collagen Type IV↗