The mechanism(s) by which neural tumor cells, specifically rat C6 glioma and rat B104 or mouse C1300 neuroblastoma cells, adhere to a model extracellular matrix--the serum-coated tissue culture dish--is being studied with special interest in formation of growth cone adhesions permitting neurite formation with neuroblastoma cells. Detachment of these cells from the dish leaves adhesion sites behind as substratum-attached material (SAM) enriched in glycosaminoglycan (GAG)-containing components, a fibronectin-like glycoprotein (Co), and cell type-specific cytoskeletal proteins. The SAM of neurite-containing cells is unique in containing an uncharacterized high molecular weight polysaccharide (Io). We will determine the SAM composition of three classes of behavioral variants of rat neuroblastoma cells under various growth and attachment conditions. Many approaches will be used to biochemically characterize the Io polysaccaride and the relatedness of the Co glycoprotein to authentic fibroblast fibronectin. The cell surface distribution of some of these components will also be studied. We will determine which of the GAG's exist in the adhesion site as proteoglycans, as well as the reversible formation of supramolecular aggregates of these proteoglycans after dissociative or associative extraction from SAM and the possible binding of Co and Io to these aggregates. Cell-type or neurite-specific aggregates will be of particular interest. These studies should help to elucidate how these two cell types of central nervous system origin adhere to one type of extracellular matrix and whether generation of neurites results from a differing biochemical interaction with the substratum.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS017139-05
Application #
3397393
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1981-04-01
Project End
1986-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Culp, L A; Lin, W C; Kleinman, N R (1999) Tagged tumor cells reveal regulatory steps during earliest stages of tumor progression and micrometastasis. Histol Histopathol 14:879-86
Culp, L A; Lin, W; Kleinman, N R et al. (1998) Earliest steps in primary tumor formation and micrometastasis resolved with histochemical markers of gene-tagged tumor cells. J Histochem Cytochem 46:557-68
Culp, L A; Lin, W C; Kleinman, N R et al. (1998) Tumor progression, micrometastasis, and genetic instability tracked with histochemical marker genes. Prog Histochem Cytochem 33:XI-XV, 329-48
Judware, R; Culp, L A (1997) N-myc over-expression downregulates alpha3beta1 integrin expression in human Saos-2 osteosarcoma cells. Clin Exp Metastasis 15:228-38
Judware, R; Culp, L A (1997) Concomitant down-regulation of expression of integrin subunits by N-myc in human neuroblastoma cells: differential regulation of alpha2, alpha3 and beta1. Oncogene 14:1341-50
Judware, R; Culp, L A (1995) Over-expression of transfected N-myc oncogene in human SKNSH neuroblastoma cells down-regulates expression of beta 1 integrin subunit. Oncogene 11:2599-607
Judware, R; Lechner, R; Culp, L A (1995) Inverse expressions of the N-myc oncogene and beta 1 integrin in human neuroblastoma: relationships to disease progression in a nude mouse model system. Clin Exp Metastasis 13:123-33
Flickinger, K S; Judware, R; Lechner, R et al. (1994) Integrin expression in human neuroblastoma cells with or without N-myc amplification and in ectopic/orthotopic nude mouse tumors. Exp Cell Res 213:156-63
Kleinman, N R; Lewandowska, K; Culp, L A (1994) Tumour progression of human neuroblastoma cells tagged with a lacZ marker gene: earliest events at ectopic injection sites. Br J Cancer 69:670-9
Lewandowska, K; Pergament, E; Sukenik, C N et al. (1992) Cell-type-specific adhesion mechanisms mediated by fibronectin adsorbed to chemically derivatized substrata. J Biomed Mater Res 26:1343-63

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