Biomedical subjects

C E Klein

Publications and source records attributed to C E Klein.

57 records · Page 4Linked to original sources

PubMed1980

Differential effects of noxious and non-noxious input on neurones according to location in ventral periaqueductal grey or dorsal raphe nucleus.

Nociceptive and non-nociceptive input to the dorsal raphe nucleus (DR) and to the surrounding periaqueductal grey (PAG) was studied in chloralose-anaesthetized rats. Single units in the midbrain responding to electrical stimulation of a coccygeal nerve were recorded with glass micropipettes. A fluorescence histochemical technique was applied to identify recording sites in the DR and PAG. 109 DR-units, 141 PAG-units and 95 units from surrounding structures were tested for responsiveness to electrical nerve stimulation. In 53% of the DR-units, but in only 20% of the PAG- and SN-units, ongoing activity was inhibited by electrical stimulation (I-units) while 42% of the PAG- and SN-units but only 24% of the DR-units were electrically excited (E-units). 40 E-units and 24 I-units were tested with repeated noxious radiant heat stimuli applied to the tail or hindpaws. 70% of the E-units were excited by heating, and in 54% of the I-units ongoing activity was inhibited by heating. The majority of the former units were located in the PAG, and most of the latter were proven to be DR-neurones. In 75% of the E-units and in 12.5% of the I-units the heat effect was in the opposite direction. The findings are discussed in terms of the now well-established role of the PAG-region in the descending control of pain. The properties of the PAG-E-units suggest that this system is involved in a negative feedback circuit by which pain transmission to the CNS limits itself. DR-I-units may be involved via an additional small loop with the PAG to disinhibit the activation of the PAG pain control system.

Animals↗

PubMedDate not supplied

ECM dependent and integrin mediated tumor cell migration of human glioma and melanoma cell lines under serum-free conditions.

Collagen IV, laminin and fibronectin are constituents of the cerebral extracellular matrix (ECM), which is critical in glioma cell invasion. The aim of the present study was to evaluate the integrin dependent cell-matrix interactions of two tumors with different invasive properties under matrixfree conditions. Two human glioma (GaMG, U373) and melanoma (MV3, BLM) cell lines were grown in serum free medium. Immunofluorescence microscopy of collagen IV, laminin, and fibronectin was performed. The adhesion of monolayer cells and their migration out of multicellular spheroids was quantified for these ECM components. Integrin chains known to act as laminin receptors were blocked by specific antibodies in additional migration assays. All cell lines expressed all the ECM components under serum free conditions. Tumor cell adhesion and migration in both glioma and melanoma cell lines was increased by all the ECM components, laminin being the strongest promotor of migration. However, migration was dose dependent in gliomas, whereas melanomas revealed a dose optimum of 10 micrograms/ml laminin. Antibodies against alpha 3 integrins significantly reduced migration on laminin in all cell lines, anti-beta 1 in all cell lines except U373. Anti-alpha 2 in BLM showed a strong effect, anti-alpha 6 was a stronger inhibitor in glioma than in melanoma cells. Integrins are functionally involved in tumor cell locomotion on laminin. The blocking of laminin related integrin chains markedly reduces cell motility in a varying manner between the cell lines. Moreover, different cell lines utilize different integrins as the laminin receptor.

Cell Adhesion↗

PubMedDate not supplied

Invasive behaviour of human gliomas is mediated by interindividually different integrin patterns.

BACKGROUND: Glioma invasion is still a major obstacle for successful therapy. In the past we could demonstrate that glioma invasion is mediated by different adhesion molecules of the integrin family. Here we investigated whether a common pattern of integrin profiles might be involved, potentially providing a therapeutical avenue. MATERIAL AND METHODS: Multicellular spheroids were generated out of three human cell lines (GaMG, U373, U251) and from tumor biopsies of 9 human glioblastomas. After confrontation with rat brain aggregates, functional blocking antibodies against different integrin subunits (alpha 2, alpha 3, alpha v, alpha 1, alpha v beta 3, alpha v beta 5) or four different disintegrines (kistrin, echistatin, eristostatin, flavoridin) were added. Integrin patterns of the human cell lines/specimens were determined by FACScan or immunohistochemistry. RESULTS: In cell lines, antibodies against alpha 2, alpha 3, alpha v and alpha v beta 5 effectively reduced invasion into rat brain aggregates. Little effect could be observed with the anti-beta 1- or with anti-alpha v beta 3- antibodies. In primary tumor specimens, however, a different invasion pattern in regard to its integrin dependency emerged with antibodies against the alpha 3-chain or the alpha v beta 3 integrin being the most effective. Invasion of primary tumor tissue into the brain aggregates was by far more aggressive compared to that of the cell lines. Accordingly, it was less influenced by integrin antibodies. The disintegrines affected migration of glioma cells on purified ECM substrates in a heterogeneous matter, but had no impact on tumor invasion into brain aggregates. CONCLUSION: Although invasion of human gliomas is mediated by integrins, due to the heterogeneity of its dependency on different integrins this approach seems not to be appropriate to sufficiently alter glioma invasion in a therapeutical neuro-oncological setting.

Aged↗