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PubMed2007

Hypothesis of the cause and development of neoplasms.

Cancer, in general, is considered a disease of genetic mutation. Many questions are, however, unanswered. How exactly do mutations occur in the cells? How do gene mutations interface with the cell microenvironment and macroenvironment to create cancer phenotypes? Is mutation the cause of cancer or the consequence of special adaptive responses to aging; hormonal imbalance; physical, chemical and biologic stresses and damage? What makes cancer spread in the body and invade other organs causing death to the patient? In this paper, we hypothesize that the cellular hyperexcitability via stimulation of mineral channels (e.g. sodium voltage-gated channels) and ligand excitatory receptors (e.g. glutamate and other neuron and non-neuronal excitatory receptors) could be a significant causative and pathogenic factor of cancer. Managing hyperexcitatory states of the cells through lifestyle, nutritional changes, phytochemical and pharmaceutical medications theoretically could be a prospective direction in cancer prevention and therapy.

Anti-Infective Agents↗

PubMed2006

Tumor necrosis factor alpha- and inducible nitric oxide synthase-producing dendritic cells are rapidly recruited to the bladder in urinary tract infection but are dispensable for bacterial clearance.

The role of dendritic cells (DC) in urinary tract infections (UTI) is unknown. These cells contribute directly to the innate defense against various viral and bacterial infections. Here, we studied their role in UTI using an experimental model induced by transurethral instillation of the uropathogenic Escherichia coli (UPEC) strain 536 into C57BL/6 mice. While few DC were found in the uninfected bladder, many had been recruited after 24 h, mostly to the submucosa and uroepithelium. They expressed markers of activation and maturation and exhibited the CD11b+ F4/80+ CD8- Gr-1- myeloid subtype. Also, tumor necrosis factor alpha (TNF-alpha)- and inducible nitric oxide synthase (iNOS)-producing CD11bINT DC (Tip-DC) were detected, which recently were proposed to be critical in the defense against bacterial infections. However, Tip-DC-deficient CCR2-/- mice did not show reduced clearance of UPEC from the infected bladder. Moreover, clearance was also unimpaired in CD11c-DTR mice depleted of all DC by injection of diphtheria toxin. This may be explained by the abundance of granulocytes and of iNOS- and TNF-alpha-producing non-DC that were able to replace Tip-DC functionality. These findings demonstrate that some of the abundant DC recruited in UTI contributed innate immune effector functions, which were, however, dispensable in the microenvironment of the bladder.

Animals↗

PubMed1992

GFAP-immunoreactive perivascular glia in the chick optic tectum.

Immunocytochemical staining of the glial fibrillary acidic protein (GFAP) was utilized to characterize the processes of the astrocytes enveloping the vessel wall in the central nervous system. The study was carried out in the mesencephalic lobes of 18 and 20 incubation-day chick embryos and of 20 day chickens. A perivascular GFAP positivity was mainly detectable in the vessel portions running within the tectum white layers, while it was scarce, or absent, in the grey ones. The perivascular GFAP negativity in the tectum cellular layers was not considered result of the absence of astrocytic endfeet since our previous electronmicroscopical studies evidenced an almost complete perivascular astrocytic ring throughout the tectum layers at hatching time. Present data rather suggest that the expression of the GFAP-made intermediate filaments in developing astrocytes might be controlled by the surrounding microenvironment.

Animals↗

PubMed1996

Myasthenia gravis.

Myasthenia gravis (MG) is the classical organ specific, autoantibody mediated and T cell dependent human autoimmune disease. It is almost invariably associated with pathological alterations of the thymus. These are described here with reference to distinct models of autoimmunization against the acetylcholine receptor (AChR). In MG with thymitis B cells are increased in the medulla forming germinal centers or diffuse B cell infiltrates. Intrathymic production of AChR-specific autoantibodies is the result of a classical antigen-driven immune reaction that occurs completely inside the thymus and involves AChR on myoid cells as the triggering (myasthenogenic) antigen. In thymomas no intratumorous immune reaction occurs and the AChR is not the myasthenogenic antigen. Instead, an abnormal neurofilament that shares epitopes with the AChR is expressed in thymomas and may trigger AChR-specific, non-tolerogenic T cell selection by molecular mimicry. These data support the hypothesis that initial steps in the pathogenesis of MG take place within abnormal thymic microenvironments, be they inflammatory or neoplastic. The etiology of MG remains enigmatic.

Adolescent↗

PubMed2026

Integrated single-cell and bulk transcriptomic analysis identifies a novel senescent fibroblast subtype associated with poor prognosis in acral melanoma.

BACKGROUND: Acral melanoma (AM) exhibits significant intratumoral heterogeneity, but its tumor microenvironment (TME) and immune regulation remain unclear. This study aims to dissect TME heterogeneity and establish a prognostic model based on key cell subpopulations. METHODS: We collected AM single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). Unsupervised clustering, CellChat, and Scissor analysis were performed to characterize cellular heterogeneity, cell-cell communication, and prognosis-related cell subpopulations. Kaplan-Meier analysis was used to assess the prognostic value of key genes, which were further validated by multiplex immunohistochemistry (mIHC). RESULTS: In AM, Mel_C2, C7, and C9 with high SEMA6A and KIT expression were strongly linked to poor prognosis. We further identified a senescent fibroblast subpopulation (sCAF_CDKN2A) characterized by high fibroblast senescence signature (FSS) scores. Integrating Scissor analysis of fibroblast subtypes with bulk prognostic data, we identified COL3A1, VCAN, and KIT as prognosis-associated genes upregulated in poor-outcome-related fibroblast subsets. Cell-cell communication analysis revealed that sCAF_CDKN2A engages in an immunosuppressive network, interacting with regulatory T cells (Tregs) via MIF signaling and receiving signals from exhausted CD8+ T cells through PPIA-BSG interactions. Using transcription factor expression patterns from these fibroblast subtypes, we constructed a prognostic model that effectively stratified patients into distinct risk groups with significant differences in overall survival (OS). mIHC confirmed significantly higher protein levels of SEMA6A and COL3A1 in tumor tissues compared to matched normal tissues. CONCLUSIONS: We established a novel prognostic model for AM and identified sCAF_CDKN2A as an immunosuppressive senescent fibroblast subpopulation driving poor prognosis.

Acral melanoma↗

PubMed1998

Developmental and hormonal regulation of hepatocyte growth factor expression and action in the bovine ovarian follicle.

Ovarian hormones (i.e., estrogen and LH) may promote folliculogenesis by regulating the local production of mesenchymal "inducer proteins" that mediate theca cell-granulosa cell interactions. Theca cells produce hepatocyte growth factor (HGF) that can stimulate granulosa cell growth. In order to investigate the physiological role of HGF in the ovarian follicle, the developmental and hormonal regulation of HGF was examined during follicular development in the bovine ovary. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to examine HGF expression in theca cells and the HGF receptor (HGFR or c-met) in granulosa cells. Both HGF and HGFR were detected throughout follicular development in small (< 5 mm)-, medium (5-10 mm)-, and large (> 10 mm)-sized follicles. Steady-state levels of HGF and HGFR mRNAs were determined using sensitive quantitative RT-PCR assays. Developmental regulation of HGF in theca cells and HGFR in granulosa cells was analyzed in freshly isolated small-, medium-, and large-sized follicles. Observations demonstrate that expression of HGF (in theca cells) and HGFR (in granulosa cells) was highest in large-sized follicles. Hormonal regulation of HGF was analyzed in hormone-treated theca cell cultures. Steady-state levels of HGF mRNA in theca cells were increased by treatment with hCG (an LH agonist), but estradiol had no effect. These results suggest that LH may promote ovarian follicular growth (i.e., granulosa cell proliferation) in part by stimulating the local production of HGF by theca cells. Effects of HGF on granulosa cell differentiated functions were examined. Treatment with HGF reduced basal and FSH-stimulated levels of aromatase activity in bovine and rat granulosa cells. In addition, HGF inhibited the ability of hCG to stimulate progesterone production by granulosa cells. The inhibition of granulosa cell steroid production by HGF is proposed to be the indirect effect of promoting cellular proliferation. Therefore, HGF directly stimulates granulosa cell proliferation and indirectly inhibits granulosa cell differentiated functions. The developmental and hormonal regulation of HGF and HGFR during folliculogenesis provides evidence that HGF may be important for hormone-induced granulosa cell proliferation. As a result, HGF may be essential for establishing the granulosa cell population and microenvironment required for oocyte maturation in the female.

Animals↗

PubMed2005

Pathogenesis of some neurological immune ultrastructural and morphometrical observations on rat thymus.

Numerous studies on neuro-immuno-modulation indicate that the thymus is involved in many neurological diseases, including experimental allergic encephalomyelitis (EAE). Twenty Lewis rats were induced for EAE. At X, XII, XX and XXX days post-inoculation the animals were killed, and the thymus was recovered and harvested. Specimens of thymus were submitted to morphological light microscopy analysis (1% toluidine blue) and ultra-structural analysis (transmission electron microscopy). Significant morphometric data were collected by examining the images quantitatively and by statistically analysing the values. Our results show that the microenvironment of the thymus is severally involved in acute EAE. Thymocytes and reticular epithelial cells show many changes which are closely related to the pathogenesis of EAE. In particular we observed: (1) inside the cell an increase in intra-cytoplasmic vacuoles, and changes in the thickness of the nuclear membrane, mitochondria, rough endoplasmic reticulum, cellular inter-digitations and cellular electron-density; (2) outside the cell an increase in pericellular translucent halo, intercellular spaces, intercellular contacts and apoptotic and necrotic figures. The evidence of a thymic role in MS may suggest the intriguing therapeutic concept of thymectomy in the management of this neurological disease.

Animals↗

PubMed1995

[Morphological and pathogenetic aspects of aplastic anemia].

A complex study of colony-stimulating properties of cells-precursors of granulomonocytopoiesis, morphological parameters of the marrow histological structures and immunological parameters was carried out in 90 patients to specify pathogenic mechanisms of aplastic anemia (AA) development. 95% of patients appeared to have sharp decrease of the marrow colony-stimulating properties and only 5% had normal initial indexes. In most patients endostal cell number increased, while the content of reticulocytes grew higher in more than 30% of patients. Defect of the marrow stroma functioning was registered in 23% of patients. Increase of the osseous tissue volume and osteocyte number was found. Dysbalance in cellular link of immunity was demonstrated. Only temporal increase of the marrow colony-stimulating properties was marked in some patients on the background of treatment with antilymphocyte globulin, despite the clinic-hematological improvement. Multifactor pathophysiological mechanisms, the main of which is the stem cell defect lies in the base of AA pathogenesis. Hemopoietic microenvironment pathology is not the leading reason of the hemopoiesis depression but it contributes greatly in its development. Immunological alterations in patients with AA are secondary and can be partly corrected with treatment with ALG.

Adolescent↗

PubMed1997

Effects of photodynamic therapy on glioma spheroids.

The present study describes the sensitivity of glioma cells to a haematoporphyrin derivative (Photosan-3) under laser activation (argon-pumped dye laser). The effects of photodynamic therapy (PDT) on cell growth, directional migration and cell invasion were investigated on two human glioma cell lines (GaMg and U-251 Mg). The directional cell migration and spheroid growth was determined for both cell lines exposed to increasing laser energy output (15-35J/cm2) with concentrations of 5 and 7 micrograms/ml of Photosan-3. Both cell lines showed a dose-dependent migratory response to increasing laser irradiation, that was more prominent in the 7 micrograms/ml treatment group. This effect occurred during the first 4 days after drug exposure. Also, spheroids from both cell lines showed a drug and laser output energy dose-dependent inhibition of growth which became apparent after a lag period of 6 days. The lag period was characterized by a decreased growth rate as compared with the control group. During this period the outer cell layers of the spheroids fell apart. The remaining spheroid tissue was not able to migrate and to regrow when exposed to the highest laser energy outputs (30-35J/cm2, 5 and 7 micrograms/ml Photosan-3). These spheroids showed, however, the ability for invasion when confronted with normal brain cell aggregated in vivo. Light microscopic observations of co-cultures between tumour tissue and brain cell aggregates revealed a normal tumour morphology. This indicates that the remaining tumour cells were not dead and could be stimulated to invade the normal tissue when exposed to a normal brain microenvironment.

Adult↗

PubMedDate not supplied

[Changes in the immune system of the victims of the action of the factors in the accident at the Chernobyl Atomic Electric Power Station. Their manifestations, nature and the possible sequelae].

The hypothesis is formulated, which explains genesis of long-lasting disturbances in the immune system of the persons affected by factors of Chernobyl disaster. Immunological alterations which are displayed at the late time after action of radiation in doses 0.5 Gy or lower are not a result of direct damage of the cells of immune system by irradiation. Their development is more probably a result of appearance of some systemic conditions and factors in affected organism--such as hormonal disbalance and especially autoantibodies of different specificities, including those reactive with thymic epithelial cells. Autoantibodies of the last type induce the decrease of thymic hormone secretion which results in functional deficiency of T lymphocytes. This chain of events is similar to those occurring in aging and does not directly causes development of the clinical displays of immunodeficiency. Only irradiation in doses of 4-6 Gy or higher inducing the structural damage of thymic microenvironment can rouse the long-lasting T cell immunodeficiency with the clinical manifestations.

Humans↗

PubMed1993

Population heterogeneity among cells of the megakaryocyte lineage.

Understanding the developmental steps in megakaryocyte differentiation requires information regarding the microenvironmental influences which direct or permit the growth and differentiation of these cells. The megakaryocyte microenvironment, like other lineages, is a complex structure comprised of the various megakaryocytic cells, the extracellular matrix (ECM) surrounding them, and the hematopoietic stromal cells which elaborate both growth factors and ECM. As a result, definition of the minimal essential requirements for megakaryocyte development is difficult. The intricacies of megakaryocyte development are further complicated by the cellular heterogeneity of both mature megakaryocytes and their precursors, as well as a differential responsiveness of these cells to hematopoietic growth factors. This review focuses on defining the various subpopulations of megakaryocytic cells and examining their functional distinctions and in vitro responsiveness to various stimuli.

Cell Differentiation↗

PubMed1996

The biology and application of human bone marrow stromal cell precursors.

The importance of the stromal tissue of the bone marrow in regulating hemopoiesis is well documented. However, several features of marrow stromal cell biology remain poorly understood, in particular, the ontogeny and phylogeny of the various stromal elements that comprise the microenvironment of the bone marrow. In this article we review recent data concerning the immunophenotype and functional characteristics of precursor cells for marrow stromal tissue. The study of these stromal precursor cells (SPC) represents an exciting new field of research that will almost certainly expand in the future as we gain a greater understanding of the cellular and molecular events, environmental cues, and growth factors that physiologically regulate the commitment and subsequent development of SPC. Although the field of marrow SPC biology is in its infancy, we predict that future studies will result in several novel clinical applications for SPC. We, therefore, conclude this article by speculating on a number of these potential applications and, thus, view SPC and their progeny as likely vehicles for several novel and important cellular therapies, including gene therapy.

Antineoplastic Agents↗

PubMed2006

Perk-dependent translational regulation promotes tumor cell adaptation and angiogenesis in response to hypoxic stress.

It has been well established that the tumor microenvironment can promote tumor cell adaptation and survival. However, the mechanisms that influence malignant progression have not been clearly elucidated. We have previously demonstrated that cells cultured under hypoxic/anoxic conditions and transformed cells in hypoxic areas of tumors activate a translational control program known as the integrated stress response (ISR). Here, we show that tumors derived from K-Ras-transformed Perk(-/-) mouse embryonic fibroblasts (MEFs) are smaller and exhibit less angiogenesis than tumors with an intact ISR. Furthermore, Perk promotes a tumor microenvironment that favors the formation of functional microvessels. These observations were corroborated by a microarray analysis of polysome-bound RNA in aerobic and hypoxic Perk(+/+) and Perk(-/-) MEFs. This analysis revealed that a subset of proangiogenic transcripts is preferentially translated in a Perk-dependent manner; these transcripts include VCIP, an adhesion molecule that promotes cellular adhesion, integrin binding, and capillary morphogenesis. Taken with the concomitant Perk-dependent translational induction of additional proangiogenic genes identified by our microarray analysis, this study suggests that Perk plays a role in tumor cell adaptation to hypoxic stress by regulating the translation of angiogenic factors necessary for the development of functional microvessels and further supports the contention that the Perk pathway could be an attractive target for novel antitumor modalities.

Animals↗

PubMed2002

Biologic sequelae of nuclear factor-kappaB blockade in multiple myeloma: therapeutic applications.

The transcription factor nuclear factor-kappaB (NF-kappaB) confers significant survival potential in a variety of tumors. Several established or novel anti-multiple myeloma (anti-MM) agents, such as dexamethasone, thalidomide, and proteasome inhibitors (PS-341), inhibit NF-kappaB activity as part of their diverse actions. However, studies to date have not delineated the effects of specific inhibition of NF-kappaB activity in MM. We therefore investigated the effect of SN50, a cell-permeable specific inhibitor of NF-kappaB nuclear translocation and activity, on MM cells. SN50 induced apoptosis in MM cell lines and patient cells; down-regulated expression of Bcl-2, A1, X-chromosome-linked inhibitor-of-apoptosis protein (XIAP), cellular inhibitor-of-apoptosis protein 1 (cIAP-1), cIAP-2, and survivin; up-regulated Bax; increased mitochondrial cytochrome c release into the cytoplasm; and activated caspase-9 and caspase-3, but not caspase-8. We have previously demonstrated that tumor necrosis factor-alpha (TNF-alpha) is present locally in the bone marrow microenvironment and induces NF-kappaB-dependent up-regulation of adhesion molecules on both MM cells and bone marrow stromal cells, with resultant increased adhesion. In this study, TNF-alpha alone induced NF-kappaB nuclear translocation, cIAP-1 and cIAP-2 up-regulation, and MM cell proliferation; in contrast, SN50 pretreatment sensitized MM cells to TNF-alpha-induced apoptosis and cleavage of caspase-8 and caspase-3, similar to our previous finding of SN50-induced sensitization to apoptosis induced by the TNF-alpha family member TNF-related apoptosis-inducing ligand (TRAIL)/Apo2L. Moreover, SN50 inhibited TNF-alpha-induced expression of another NF-kappaB target gene, intercellular adhesion molecule-1. Although the p38 inhibitor PD169316 did not directly kill MM cells, it potentiated the apoptotic effect of SN50, suggesting an interaction between the p38 and NF-kappaB pathways. Our results therefore demonstrate that NF-kappaB activity in MM cells promotes tumor-cell survival and protects against apoptotic stimuli. These studies provide the framework for targeting NF-kappaB activity in novel biologically based therapies for MM.

Apoptosis↗

PubMed2005

Dynamic contrast-enhanced and diffusion MRI show rapid and dramatic changes in tumor microenvironment in response to inhibition of HIF-1alpha using PX-478.

PX-478 is a new agent known to inhibit the hypoxia-responsive transcription factor, HIF-1alpha, in experimental tumors. The current study was undertaken in preparation for clinical trials to determine which noninvasive imaging endpoint(s) is sensitive to this drug's actions. Dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) were used to monitor acute effects on tumor hemodynamics and cellularity, respectively. Mice bearing human xenografts were treated either with PX-478 or vehicle, and imaged over time. DW imaging was performed at three b values to generate apparent diffusion coefficient of water (ADCw) maps. For DCE-MRI, a macromolecular contrast reagent, BSA-Gd-DTPA, was used to determine vascular permeability and vascular volume fractions. PX-478 induced a dramatic reduction in tumor blood vessel permeability within 2 hours after treatment, which returned to baseline by 48 hours. The anti-VEGF antibody, Avastin, reduced both the permeability and vascular volume. PX-478 had no effect on the perfusion behavior of a drug-resistant tumor system, A-549. Tumor cellularity, estimated from ADCw, was significantly decreased 24 and 36 hours after treatment. This is the earliest significant response of ADC to therapy yet reported. Based on these preclinical findings, both of these imaging endpoints will be included in the clinical trial of PX-478.

Animals↗

PubMed2024

Genomic and the tumor microenvironment heterogeneity in multifocal hepatocellular carcinoma.

BACKGROUND AND AIMS: Ambiguous understanding of tumors and tumor microenvironments (TMEs) hinders accurate diagnosis and available treatment for multifocal hepatocellular carcinoma (HCC) covering intrahepatic metastasis (IM) and multicentric occurrence (MO). Here, we characterized the diverse TMEs of IM and MO identified by whole-exome sequencing at single-cell resolution. APPROACH AND RESULTS: We performed parallel whole-exome sequencing and scRNA-seq on 23 samples from 7 patients to profile their TMEs when major results were validated by immunohistochemistry in the additional cohort. Integrative analysis of whole-exome sequencing and single-cell RNA sequencing found that malignant cells in IM showed higher intratumor heterogeneity, stemness, and more activated metabolism than those in MO. Tumors from IM shared similar TMEs while distinct TMEs were noticed in those from MO. Furthermore, CD20+ B cells, plasma cells, and conventional type II dendritic cells (cDC2s) were decreased in IM relative to MO while T cells in IM exhibited a more terminally exhausted capacity with a higher proportion of proliferative/exhausted T cells than that in MO. Both CD20 and CD1C correlated with better prognosis in multifocal HCC. Additionally, MMP9+ tumor-associated macrophages were enriched across IM and MO, which formed cellular niches with regulatory T cells and proliferative/exhausted T cells. CONCLUSIONS: Our findings deeply decipher the heterogeneous TMEs between IM and MO, which provide a comprehensive landscape of multifocal HCC.

Humans↗

PubMed1996

Comparison of the growth and fate of fetal spinal iso- and allografts in the adult rat injured spinal cord.

Most studies investigating early fetal CNS graft-host interactions and host immune responses have been performed using intracerebral transplantation paradigms. The purpose of this study was to establish the early developmental dynamics of fetal graft integration with the injured host spinal cord and to determine whether fetal allografts in this environment are subject to rejection. ACI rat fetal spinal cord (FSC) tissue was grafted into acute lesion cavities of adult WF rat spinal cords. Graft development and/or rejection was followed from 1 to 45 days posttransplantation with morphometric, histological, and immunocytochemical methods. We determined that all FSC grafts in acute resection lesions of the adult rat spinal cord undergo an early substantial cellular attrition, but following favorable attachment to healthy host tissue margins, they rebound and grow to fill the lesion cavity by approximately 45 days. We also determined that FSC allografts into nonimmunosuppressed adult recipients are consistently rejected, but only after an early period of growth and maturation. The onset of rejection is characterized by extensive cellular infiltration coincidental with graft and host MHC antigen expression. The implications of delayed graft development and graft-host integration are discussed relative to interconnectivity and long-term potential for graft-derived benefits. The observed rejection response was characteristic of first-order allograft rejection and underscores a lack of immunological privilege in the microenvironment of the injured spinal cord.

Age Factors↗

PubMed2000

Role of the extracellular matrix during neural crest cell migration.

Once specified to become neural crest (NC), cells occupying the dorsal portion of the neural tube disrupt their cadherin-mediated cell-cell contacts, acquire motile properties, and embark upon an extensive migration through the embryo to reach their ultimate phenotype-specific sites. The understanding of how this movement is regulated is still rather fragmentary due to the complexity of the cellular and molecular interactions involved. An additional intricate aspect of the regulation of NC cell movement is that the timings, modes and patterns of NC cell migration are intimately associated with the concomitant phenotypic diversification that cells undergo during their migratory phase and the fact that these changes modulate the way that moving cells interact with their microenvironment. To date, two interplaying mechanisms appear central for the guidance of the migrating NC cells through the embryo: one involves secreted signalling molecules acting through their cognate protein kinase/phosphatase-type receptors and the other is contributed by the multivalent interactions of the cells with their surrounding extracellular matrix (ECM). The latter ones seem fundamental in light of the central morphogenetic role played by the intracellular signals transduced through the cytoskeleton upon integrin ligation, and the convergence of these signalling cascades with those triggered by cadherins, survival/growth factor receptors, gap junctional communications, and stretch-activated calcium channels. The elucidation of the importance of the ECM during NC cell movement is presently favoured by the augmenting knowledge about the macromolecular structure of the specific ECM assembled during NC development and the functional assaying of its individual constituents via molecular and genetic manipulations. Collectively, these data propose that NC cell migration may be governed by time- and space-dependent alterations in the expression of inhibitory ECM components; the relative ratio of permissive versus non-permissive ECM components; and the supramolecular assembly of permissive ECM components. Six multidomain ECM constituents encoded by a corresponding number of genes appear to date the master ECM molecules in the control of NC cell movement. These are fibronectin, laminin isoforms 1 and 8, aggrecan, and PG-M/version isoforms V0 and V1. This review revisits a number of original observations in amphibian and avian embryos and discusses them in light of more recent experimental data to explain how the interaction of moving NC cells with these ECM components may be coordinated to guide cells toward their final sites during the process of organogenesis.

Animals↗