Biomedical subjects

A Lochter

Publications and source records attributed to A Lochter.

23 records · Page 2Linked to original sources

PubMed1995

Involvement of extracellular matrix constituents in breast cancer.

It has recently been established that the extracellular matrix is required for normal functional differentiation of mammary epithelia not only in culture, but also in vivo. The mechanisms by which extracellular matrix affects differentiation, as well as the nature of extracellular matrix constituents which have major impacts on mammary gland function, have only now begun to be dissected. The intricate variety of extracellular matrix-mediated events and the remarkable degree of plasticity of extracellular matrix structure and composition at virtually all times during ontogeny, make such studies difficult. Similarly, during carcinogenesis, the extracellular matrix undergoes gross alterations, the consequences of which are not yet precisely understood. Nevertheless, an increasing amount of data suggests that the extracellular matrix and extracellular matrix-receptors might participate in the control of most, if not all, of the successive stages of breast tumors, from appearance to progression and metastasis.

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PubMed1994

The extracellular matrix molecule janusin regulates neuronal morphology in a substrate- and culture time-dependent manner.

Janusin is an extracellular matrix glycoprotein with structural homology to tenascin. In search of extracellular matrix components which govern the differentiation of neurons in the central nervous system, we have investigated the influence of janusin on the differentiation of hippocampal neurons in vitro. Janusin coated onto nitrocellulose was a good substrate for attachment of cell bodies and neurite outgrowth after 21 h of culture. Most cells exhibited a polarized morphology with one long major neurite and one or two short minor neurites. When janusin was coated onto a polyornithine-conditioned plastic surface, it increased the polarity of neurons in that the length of major neurites was increased and the length and number of minor neurites were decreased when compared with the control polyornithine-conditioned plastic without janusin. As we have shown before for tenascin, laminin and fibronectin, polarization was preceded by an increase in the number and length of all neurites during the first hours after cell plating. This study therefore adds janusin to the increasing number of extracellular matrix glycoproteins which promote axonal but not dendritic growth.

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PubMed1994

Isolation of a neural chondroitin sulfate proteoglycan with neurite outgrowth promoting properties.

Proteoglycans are expressed in various tissues on cell surfaces and in the extracellular matrix and display substantial heterogeneity of both protein and carbohydrate constituents. The functions of individual proteoglycans of the nervous system are not well characterized, partly because specific reagents which would permit their isolation are missing. We report here that the monoclonal antibody 473HD, which binds to the surface of early differentiation stages of murine astrocytes and oligodendrocytes, reacts with the chondroitin sulfate/dermatan sulfate hybrid epitope DSD-1 expressed on a central nervous system chondroitin sulfate proteoglycan designated DSD-1-PG. When purified from detergent-free postnatal days 7 to 14 mouse brain extracts, DSD-1-PG displays an apparent molecular mass between 800-1,000 kD with a prominent core glycoprotein of 350-400 kD. Polyclonal anti-DSD-1-PG antibodies and monoclonal antibody 473HD react with the same molecular species as shown by immunocytochemistry and sequential immunoprecipitation performed on postnatal mouse cerebellar cultures, suggesting that the DSD-1 epitope is restricted to one proteoglycan. DSD-1-PG promotes neurite outgrowth of embryonic day 14 mesencephalic and embryonic day 18 hippocampal neurons from rat, a process which can be blocked by monoclonal antibody 473HD and by enzymatic removal of the DSD-1-epitope. These results show that the hybrid glycosaminoglycan structure DSD-1 supports the morphological differentiation of central nervous system neurons.

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PubMed1993

Tenascin and extracellular matrix glycoproteins: from promotion to polarization of neurite growth in vitro.

The extracellular matrix molecules tenascin, laminin, and fibronectin, the cell adhesion molecule L1, and the lectin concanavalin A (ConA) were tested for their effects on neuritogenesis in cultures of hippocampal neurons. We analyzed neurite outgrowth between 3 and 21 hr after plating and found that, on polyornithine as control substrate, lengths of axon-like major neurites and dendrite-like minor neurites increased continuously with time in culture. Moreover, growth of minor neurites was faster than growth of major neurites. When the extracellular matrix molecules tenascin, laminin, and fibronectin were coated on polyornithine substrates, growth of all neurites was faster than on control substrates during the first hours of culture. After this initial phase of enhanced neurite outgrowth, elongation of major neurites continued at a higher rate than on the control substrate and growth of minor neurites ceased after 12 hr. Correspondingly, neuronal polarity was strongly increased on the extracellular matrix substrates during later phases of culture. In contrast, lengths of both major and minor neurites were increased over control values on L1 and ConA substrates at all time points investigated. Thus, neuronal polarity was similar for control, L1, and ConA substrates. Spreading of neuronal cell bodies was reduced by about 50% on tenascin, laminin, and fibronectin and by less than 20% on L1 and ConA substrates after 21 hr of culture, when compared to the control substrate. Neuron-to-substrate adhesion was reduced on all three extracellular matrix substrates but not affected on L1 or ConA substrates, after 3 and 21 hr of culture. These observations indicate that induction of neuronal polarity is not a general feature of neurite outgrowth-promoting molecules, such as L1 or ConA, but a distinctive property of the three extracellular matrix glycoproteins studied, and may suggest that enhancement of polarity is correlated with decreased strength of adhesion.

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PubMed1991

J1/tenascin in substrate-bound and soluble form displays contrary effects on neurite outgrowth.

The influence of J1/tenascin adsorbed to polyornithine-conditioned plastic (substrate-bound J1/tenascin) and J1/tenascin present in the culture medium (soluble J1/tenascin) on neurite outgrowth was studied with cultured single cells from hippocampus and mesencephalon of embryonic rats. Neurons at low density grew well on J1/tenascin substrates and extended neurites that were approximately 40% longer than on the polyornithine control substrate after 24 h in vitro. The neurite outgrowth promoting effect of substrate bound J1/tenascin was largely abolished in the presence of mAb J1/tn2, but not by mAb J1/tn1. In contrast to the neurite growth-promoting effects of substrate bound J1/tenascin, neurite outgrowth on polyornithine, laminin, fibronectin, or J1/tenascin as substrates was inhibited by addition of soluble J1/tenascin to the cultures. Neither of the two mAbs neutralized the neurite outgrowth-inhibitory properties of soluble J1/tenascin. In contrast to their opposite effects on neurite outgrowth, both substrate-bound and soluble J1/tenascin reduced spreading of the neuronal cell bodies, suggesting that the neurite outgrowth-promoting and antispreading effects are mediated by two different sites on the molecule. This was further supported by the inability of the mAb J1/tn2 to neutralize the antispreading effect. The J1/tn2 epitope localizes to a fibronectin type III homology domain that is presumably distinct from the putative Tn68 cell-binding domain of chicken tenascin for fibroblasts, as shown by electronmicroscopic localization of antibody binding sites. We infer from these experiments that J1/tenascin contains a neurite outgrowth promoting domain that is distinguishable from the cell-binding site and presumably not involved in the inhibition of neurite outgrowth or cell spreading. Our observations support the notion that J1/tenascin is a multifunctional extracellular matrix molecule.

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