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Biomedical subjects

M T Armstrong

Publications and source records attributed to M T Armstrong.

17 recordsLinked to original sources
PubMed2000

Intercellular invasion and the organizational stability of tissues: a role for fibronectin.

Intracellular invasion is the movement of cells of one type into the fabric of other, contiguous tissues. Invasion is a signature behavior of the malignant tumor and also is found as part of the normal behavior of inflammatory blood cells and tissues engaged in the morphogenetic movements of normal embryogenesis and in a number of instances of normal and pathological tissue remodeling in the adult. Informed by the view that the underlying mechanisms of invasion will be similar for tumor cells and invasive blood and embryonic cells, this review adopts a comparative approach to the analysis of invasion. Invasion results in the development of a diffuse interface between contiguous tissues. Its alternative is the maintenance of stable, planar tissue boundaries. This is the more usual condition for contiguous tissues in the animal. This review will focus on the processes that, on the one hand, stabilize planar contact interfaces between tissues, and, on the other, promote the destabilization of tissue integrity by fostering intercellular invasion. Particular attention is devoted to a role for adhesive interactions mediated by the matrix adhesion molecule, fibronectin. In certain instances, fibronectin in the matrix promotes invasion whereas in others, the presence of fibronectin prevents invasion. The distinction appears to depend on whether the invasive tissue is migrating into an acellular extracellular matrix or whether invasion involves densely cellular tissues. In the first instance, fibronectin promotes invasion, whereas in the second, it stabilizes the interface of the contacting tissues and prevents invasion.

Animals↗
PubMed2000

Regulation of proliferation of the fetal myocardium.

Growth of the myocardium involves the completion of a fixed number of rounds of cell division during the embryonic and fetal stages followed by entry into a postmitotic state and hypertrophy of the postmitotic cardiomyocytes during the later stages of heart growth. It has been suggested that at the time of its determination in the early embryo, the embryonic myocardium is programmed for a fixed and limited number of cell divisions, after which the transition to the postmitotic state occurs autonomously. The proliferative response of cultured myocardium of the fetal chick was explored in four culture settings: monolayer cell culture, collagen lattice culture, organ culture of reaggregated cardiomyocyte tissue (cardiomyocyte spheroid culture), and organ culture of pieces of the ventricle wall. Several growth factors were identified by their ability to stimulate DNA synthesis in cardiomyocytes, identified by the incorporation of 5-bromodeoxyuridine (BrdU). The serine proteases thrombin and trypsin, fibroblast growth factor-2 (FGF-2), transforming growth factor-alpha (TGF-alpha), and insulin-like growth factor-II (IGF-II) all show growth factor activity but only for cardiomyocytes cultured in three-dimensional myocardial tissue, and not for cardiomyocytes maintained in monolayer cell culture. Thus, during its proliferation phase, the growth of the fetal myocardium is not controlled solely by internal, cell-autonomous programs, but is subject to external regulation by a family of peptide growth factors. The unconventional setting of three-dimensional culture of the myocardium is required to demonstrate its responsiveness to growth factor challenge.

Animals↗
PubMed1999

Bisdiamine inhibits extracellular matrix formation and cell proliferation of atrioventricular mesenchyme from developing chick heart valves.

Abnormalities of the cushion tissues lead to atrioventricular septal defects (AVSD) and truncus arteriosus (TA). Bisdiamine exposure in the embryo frequently causes AVSD and TA in the newborn chick, mouse, or rat. We studied the effects of bisdiamine on mesenchymal cells grown in aggregate culture isolated from the developing atrioventricular valves of the stage-36 chick embryo. Fibronectin extracellular matrix formation and cell proliferation in the aggregates were assessed in various media. Chick serum stimulated the cells to produce an extracellular matrix and to divide, and the inclusion of bisdiamine inhibited both responses. If we isolated an extracellular matrix from a monolayer of mesenchymal cells and added the sonicated matrix to the medium containing serum and bisdiamine, the matrix incorporated into the aggregates and the cells entered the mitotic cycle. Our previous work established that cells need to attach to an intact extracellular matrix to begin cell division. Thus, we suggest that bisdiamine inhibits the normal formation of the extracellular matrix, leading to reduced cell proliferation, but it does not affect matrix-cell interaction. The lack of cushion growth in situ may be the cause of AVSD or TA.

Animals↗
PubMed1996

Fibroblast growth factor-2 stimulates embryonic cardiac mesenchymal cell proliferation.

The proliferation response of stage 36 chick atrioventricular valve mesenchymal cells to fibroblast growth factor-2 (FGF-2) was studied in the tissue-like environment of three-dimensional cell aggregates maintained in organ culture. The mitogenic effects of FGF-2 on mesenchymal tissue depended on the FGF-2-stimulated formation of a fibronectin-containing extracellular matrix. The matrix was absent in unstimulated aggregates, and co-localized with regions of actively proliferating cells in stimulated aggregates. Inhibition of fibronectin matrix formation by the inclusion of Arg-Gly-Asp-containing peptides, which compete with fibronectin for binding to the cell surface alpha 5 beta 1 integrin receptors, abolished the proliferation effects of FGF-2. Inhibition of sulfation of cell surface glycosaminoglycans by treatment with sodium chlorate significantly reduced both the formation of the fibronectin matrix and cell proliferation in response to FGF-2, suggesting an involvement of the low-affinity sulfated glycosaminoglycan FGF receptor system. Thus, the FGF-stimulated growth of embryonic atrioventricular valve mesenchyme in vitro involves the production of a fibronectin matrix. We suggest that the stimulation of the fibronectin matrix represents an essential element in growth factor signaling of mesenchymal tissue, with the matrix serving as an anchorage substratum for the proliferating cells.

Animals↗
PubMed1996

Thrombin stimulation of matrix fibronectin.

Trypsin, thrombin, and peptide analogues of the new amino terminus of the proteolyzed thrombin receptor, SFLLRN and SFLLRNPNDKYEPF, stimulated embryonic fibroblasts cultured as 3-dimensional tissue-like aggregates to elaborate a fibronectin-rich extracellular matrix. Enzymatically inactive thrombin and the control peptide FLLRN failed to stimulate matrix production. The induction of cell proliferation correlated with production of the fibronectin matrix. The regions of active cell proliferation in the fibroblast aggregates co-localized with the matrix and peptide analogues of the RGD cell-adhesion site of fibronectin reversibly inhibited the accumulation of the fibronectin matrix and the stimulation of cell proliferation by SFLLRN. Two different preparations of the fibronectin matrix stimulated cell proliferation in aggregates cultured in growth factor-free medium. We suggest that the stimulation of matrix production is a necessary event for mitogenic signaling in mesenchymal tissue. The tight coupling between the matrigenic and mitogenic activities of growth factors was absent in monolayer cultures of chick embryonic fibroblasts since thrombin and trypsin induced proliferation of monolayer-cultured cells without inducing the production of a fibronectin matrix.

Amino Acid Sequence↗
PubMed1993

Involvement of alpha 2-macroglobulin and C-reactive protein in a complement-like hemolytic system in the arthropod, Limulus polyphemus.

Homologues of two plasma proteins of vertebrates, alpha 2-macroglobulin and C-reactive protein, participate in a hemolytic system of the ancient arthropod, Limulus polyphemus. C-reactive protein, which can under the appropriate circumstances activate the classical pathway of the mammalian complement system, is an essential element of the hemolytic system of Limulus. The selective removal of C-reactive protein from the plasma with phosphorylethanolamine-agarose inactivated hemolysis. Addition of affinity-purified C-reactive protein to inactive plasma restored activity. Exposure of plasma to phosphorylethanolamine in solution potentiated hemolysis. alpha 2-Macroglobulin is a member of the same protein family as the complement protein C3 and both require an intact thiol ester for activity. Treatment of Limulus plasma with methylamine under conditions that inactivate thiol-ester-containing proteins reduced the hemolytic activity of some plasma preparations. Addition of purified Limulus alpha 2-macroglobulin to the methylamine-treated plasma restored hemolytic activity. However, alpha 2-macroglobulin is not necessary for hemolysis since the hemolytic activity of some pooled plasma preparations was insensitive to methylamine treatment under conditions that inactivated alpha 2-macroglobulin. Purified C-reactive protein was hemolytic in the absence of alpha 2-macroglobulin. These observations suggest that the proteins in Limulus plasma that participate in hemolysis represent the components of an ancient invertebrate defense system with distant evolutionarily affinities to the vertebrate complement system.

Animals↗
PubMed1992

Mechanisms of epibolic tissue spreading analyzed in a model morphogenetic system. Roles for cell migration and tissue contractility.

The processes responsible for epithelial spreading during wound healing and embryonic morphogenesis were investigated in an organ culture model in which an epithelial tissue (chick embryo pigmented retinal epithelium) spread over the surface of an aggregate of mesenchyme cells (chick embryo cardiac mesenchyme). The heart mesenchyme aggregate is differentiated into a core of stellate cells associated with a fibronectin-poor matrix surrounded by a cortical zone, 2-5 cells in thickness, of flattened cells embedded in a fibronectin-rich extracellular matrix. Envelopment of the mesenchyme aggregate is accompanied by a movement of the cells and the fibronectin-rich extracellular matrix of the cortex over the core tissue in advance of the spreading pigmented retina tissue. Three distinct processes were identified as contributing to epithelial spreading in this system: (1) active migration of the pigmented retinal epithelium; (2) active contraction of the cortical cells of the mesenchyme aggregate to tow the attached epithelial tissue over the mesenchyme aggregate; and (3) ingression of surface-located cells of the mesenchyme aggregate to decrease the exposed surface area by decreasing the number of cells at the surface.

Animals↗
PubMed1991

Transforming growth factor-beta 1 localized within the heart of the chick embryo.

Transforming growth factor-beta 1 is a pleiotropic peptide mediator of growth, differentiation, and extracellular matrix synthesis. In the embryonic chick heart prior to the formation of the endocardial cushions, evidence from in vitro experiments suggests that transforming growth factor-beta 1 may be an inducer of the differentiation of atrioventricular endothelial cells into endocardial cushion mesenchyme. Further in vitro evidence suggests that the factor stimulates mesenchymal cell proliferation, and, thus, growth of the cushions. Using an antibody made against a peptide duplicating the aminoterminal 30 amino acid sequence of transforming growth factor-beta 1, we stained sections of stage 11, 18, 23, 26, and 36 chick hearts by an in situ immunofluorescence technique. Transforming growth factor-beta 1 staining localized to the endocardial surface and epicardial surface of the stage 11 heart, but it decreased from these locations in later stages. The cardiac jelly (stage 11), endocardial cushions (stage 18, 23, and 26), and, subsequently, the heart valve leaflets (stage 36) stained intensely for the growth factor.

Animals↗
PubMed1990

Regulation of proliferation of embryonic heart mesenchyme: role of transforming growth factor-beta 1 and the interstitial matrix.

Proliferation of atrioventricular cushion mesenchyme of the embryonic avian heart maintained in three-dimensional aggregate culture is stimulated by interaction with the interstitial matrix. Chicken serum or transforming growth factor-beta 1, which stimulates proliferation, induces matrix deposition in regions of the aggregate showing high labeling indices with tritiated thymidine. Dispersed heart mesenchyme interstitial matrix introduced into serum-free culture is incorporated into the aggregate and stimulates cellular proliferation similar to serum or transforming growth factor-beta 1. Proliferation is reversibly inhibited by the peptide Gly-Arg-Gly-Asp-Ser-Pro. It is suggested that transforming growth factor-beta 1 stimulates the production of interstitial matrix and that a sufficient stimulus for proliferation in this system is the presence of the matrix, which acts as the adhesive support for cellular anchorage.

Animals↗
PubMed1990

An instructive role for the interstitial matrix in tissue patterning: tissue segregation and intercellular invasion.

Intercellular invasion is the intrusion of the cells of one tissue into space occupied by a second tissue. The alternative situation to invasion, one characteristic of most coherent tissues, is segregation, with identifiable boundaries existing between contiguous tissues. The interfaces between mesenchymal and myocardial tissues in the developing avian heart show a profoundly different character in different regions of the heart: the interface between epicardial mesenchyme and heart wall myocardium is planar, without intermingling of the two cell types, whereas the interface between endocardial cushion mesenchyme and myocardium is diffuse, with extensive invasion of both tissue types across the border to produce intermingling of the two tissues. Thus, invasion and tissue segregation coexist in different regions of the mesenchyme-myocardium contact zone. Investigation of the involvement of the interstitial matrix in invasion and segregation has been conducted by maintaining the two tissues in mutual contact in organ culture. Investigation of the mechanisms by which the two cell types sort out in randomized chimeric tissue reaggregates has provided insight into the conditions for tissue segregation. We have modeled invasion in organ culture by fusing aggregates of myocardial cells with aggregates of cardiac mesenchymal cells. Cells of both tissues invaded the partner aggregate during a period of 1-3 d of coculture. Both invasion and segregation in the aggregates appear to depend on the presence or absence of a fibronectin-rich interstitial matrix elaborated by the cardiac mesenchyme. During sorting, the matrix appears selectively in regions occupied by the mesenchyme. Under conditions of culture that are nonpermissive for matrix deposition, sorting fails to occur. Stimulation of matrix deposition by addition of serum, transforming growth factor beta, or isolated matrix itself is accompanied by sorting out of the two tissues. Sorting out is blocked reversibly by inclusion of the fibronectin adhesion site peptide, GRGDSP. Invasion of fused aggregates is preceded by a redistribution of the fibronectin-containing matrix of the mesenchymal aggregate such that matrix-poor regions come to occupy the interface with the myocardial partner aggregate. The invasion that ensues involves mesenchymal cells emigrating from, and myocardial cells intruding into, matrix-poor regions of the mesenchymal aggregate.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1984

A role for fibronectin in cell sorting.

A useful approach to the investigation of embryonic morphogenesis is the study of the factors that control cell movement in cell aggregates in organ culture. Previous studies, in which aggregates of embryonic chick heart ventricle tissue were paired in organ culture, supported the hypothesis that the associative behaviour is dominated by the mesenchymal cell (at the stages used the ventricle is composed of approximately 25% mesenchyme (Mes) and 75% myocyte tissue (My)) by virtue of this cell's ability to establish a pericellular matrix rich in fibronectin. In aggregate pairs, the aggregate types that develop a fibronectin-rich matrix rapidly are spread over by the aggregate types that are less able to deposit fibronectin in the matrix. In sorting conditions, Mes sorts to the surface of My. This is explained as a consequence of a requirement that Mes have access to a component in the serum fraction of the culture medium for deposition of fibronectin in the matrix. It is proposed that the factor penetrates to a shallow depth in aggregates, limiting the establishment of a fibronectin-rich matrix to superficially located Mes. As fibronectin appears in the matrix, Mes becomes more cohesive than My, allowing it to exclude myocytes and establish itself as a pure tissue that increases in volume as mesenchyme cells migrating within the interior contact the surface zone, becoming immobilized and also activated to secrete fibronectin. The analysis presented includes an experimental investigation of the different elements of this hypothesis and also explores some of the predictions of the hypothesis.

Animals↗
PubMed1981

Immunofluorescent histological studies of the role of fibronectin in the expression of the associative preferences of embryonic tissues.

The identity of the chemical factors controlling the spreading behaviour of sheets of cells was examined in organ culture. When aggregates of two dissimilar tissues are apposed in organ culture, one tissue spreads reproducibly over the surface of the second. The present study employed indirect immunofluorescent localization techniques to evaluate the hypothesis that the spreading behaviour of chick embryonic heart tissue in culture is dominated by the presence or absence of the cell-surface and extracellular matrix protein fibronectin in the surface layers of the aggregates. Specifically, the hypothesis proposes that aggregates that display surface fibronectin earlier after culturing and/or in higher quantities segregate internally to aggregates that are slower to develop a surface layer of fibronectin or in which this layer contains reduced amounts of fibronectin. The hypothesis has been supported for 3 categories of behaviour of chick embryo heart tissue: (1) myocyte aggregates spread over myocyte aggregates containing a 20% admixture of heart fibroblasts, which in turn spread over heart fibroblast aggregates; (2) 5-day embryonic ventricle-tissue fragments maintained in culture for 0.5 days spread over ventricle fragments cultured for 2.5 days; and (3) 2-day embryonic ventricle spreads over 5-day ventricle. In all these situations, the aggregate type that segregates to an internal position displays more fibronectin at its surface than aggregate types that spread to occupy an external position. Evidence is presented that the fibronectin in heart tissue aggregates is elaborated by heart fibroblasts.

Animals↗
PubMed1978

Cell motility in fibroblast aggregates.

The stable arrangements of cells in tissues and organs require that most tissue cells, whatever their inherent abilities for active pseudopod-directed locomotion, remain confined to the boundaries of their parent tissues and organs for the lifetime of the organism. Contact inhibition of motility represents a potential mechanism for immobilizing cells in tissues and thus in promoting positional stability. In order to assess the effectiveness of contact inhibition in immobilizing cells in 3-dimensional tissue-like masses, spherical aggregates of chick heart, sclera and skin fibroblasts were fused with tritiated thymidine-labelled aggregates of the identical cell type. After being placed in contact, the 2 aggregates cohere and broaden the area of mutual contact to form a single aggregate with a planar interface between the two. Mobility of cells was detected by the migration of labelled cells across the interface and into the unlabelled aggregate. Based on measurements of distances moved in day-old aggregate pairs, it was found that fibroblasts moved up to 17 cell diameters and up to 36% as far in solid tissue masses as in monolayer culture under optimal conditions for directed migration.

Animals↗