scholarly journals The Lysine-rich C-terminal Tail of Heparin Affin Regulatory Peptide Is Required for Mitogenic and Tumor Formation Activities

2001 ◽  
Vol 276 (15) ◽  
pp. 12228-12234 ◽  
Author(s):  
Isabelle Bernard-Pierrot ◽  
Jean Delbé ◽  
Danièle Caruelle ◽  
Denis Barritault ◽  
José Courty ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Biological Activities ◽  
Chinese Hamster ◽  
Tumor Formation ◽  
Cellular Growth ◽  
Heparin Binding ◽  
Regulatory Peptide ◽  
Peptide Cleavage ◽  
Terminal Domain

Heparin affin regulatory peptide (HARP) is a 18-kDa heparin-binding polypeptide that is highly expressed in developing tissues and in several primary human tumors. It seems to play a key role in cellular growth and differentiation.In vitro, HARP displays mitogenic, angiogenic, and neurite outgrowth activities. It is a secreted protein that is organized in two β-sheet domains, each domain containing a cluster of basic residues. To assess determinants involved in the biological activities of HARP, C-terminally truncated proteins were produced in Chinese hamster ovary-K1 cells and tested for their mitogenic, tumor formation in nude mice and neurite outgrowth activities. Our data clearly indicate that the residues 111–136 of the lysine-rich C-terminal domain are involved in the mitogenic and tumor formation activities of HARP. Correlatively, no signal transduction was detected using the corresponding mutant, suggesting the absence of HARP binding to its high affinity receptor. However, this C-terminal domain of HARP is not involved in the neurite outgrowth activity. We also demonstrate that HARP signal peptide cleavage could led to two maturated forms that are both but differentially mitogenic.

Suppression of tumor formation in vivo by expression of the JE gene in malignant cells

1991 ◽  
Vol 11 (6) ◽  
pp. 3125-3131
Author(s):  
B J Rollins ◽  
M E Sunday
Keyword(s):  
Cho Cells ◽  
Chinese Hamster ◽  
Suppressive Effect ◽  
Tumor Formation ◽  
Host Animal ◽  
Early Growth Response ◽  
Discernible Effect ◽  
Early Growth Response Gene

The early growth response gene JE encodes a monocyte chemoattractant, MCP-1. The JE/MCP-1 protein attracts and stimulates human monocytes and induces monocyte-mediated inhibition of tumor cell growth in vitro. Expression of human or murine JE/MCP-1 in Chinese hamster ovary (CHO) cells completely suppressed their ability to form tumors in nude mice. Coinjection of JE/MCP-1-expressing cells with nonexpressing CHO cells or with HeLa cells also prevented tumor formation. Since JE/MCP-1 expression had no discernible effect on the tranformed phenotype of these cells in vitro, the suppressive effect depends on host animal factors. These factors are likely to be components of the inflammatory response, because JE/MCP-1-expressing cells elicited a predominantly monocytic infiltrate at the site of injection. Our results suggest that JE/MCP-1 protein may be useful in cancer therapy.

Secreted-Osteopontin Contributes to Brown Adipogenesis In Vitro via a CD44-Dependent Pathway

2019 ◽  
Vol 51 (11) ◽  
pp. 741-748
Author(s):  
Mengxi Wang ◽  
Yaoyao Guo ◽  
Yumeng Zhou ◽  
Wanwan Yuan ◽  
Huixia Li ◽  
...  
Keyword(s):  
Lipid Droplets ◽  
Biological Activities ◽  
Tumor Formation ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Protein Levels ◽  
Infected Cells ◽  
Oil Red O Staining ◽  
Oil Red O

AbstractOsteopontin (OPN), a secreted glycoprotein, is involved in various pathophysiological processes including immune response, inflammation, tumor formation, and metabolism. OPN exists in 2 forms, secreted-OPN (sOPN) and intracellular-OPN (iOPN). While they might have different biological activities, it remains largely unknown whether sOPN and iOPN induce the differentiation of brown adipocytes. To test this possibility, 3T3-L1 cells were induced by DMI induction with or without recombinant human OPN (rhOPN, 10, 50, 100, 200 μM), respectively. Meanwhile, another batch of 3T3-L1 cells were infected with Ad-GFP-ap2-OPN and followed by DMI differentiation. Subsequently, the infected cells were treated with either anti-CD44 antibody or immunoglobulin G (Ig G). Accumulation of lipid droplets was visualized by Oil red O staining and protein levels were assayed by western blotting analysis. The results showed that sOPN and not rhOPN, notably increased the accumulation of lipid droplets and the expression of brown adipocyte-related genes. Moreover, neutralization of CD44 partially abrogated the effects induced by sOPN. These data demonstrate that sOPN and not rhOPN has the capacity to induce the differentiation of white preadipocytes into brown adipocytes through a CD44-dependent mechanism. The findings might provide a potential target for sOPN to combat obesity.

VACM-1, a cul-5 gene, inhibits cellular growth by a mechanism that involves MAPK and p53 signaling pathways

2003 ◽  
Vol 285 (6) ◽  
pp. C1386-C1396 ◽  
Author(s):  
C. Van Dort ◽  
P. Zhao ◽  
K. Parmelee ◽  
B. Capps ◽  
A. Poel ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cellular Proliferation ◽  
Phosphorylation Site ◽  
Chinese Hamster ◽  
Inhibitory Effect ◽  
Cellular Growth ◽  
P53 Expression ◽  
Mapk Phosphorylation ◽  
P53 Signaling

Vasopressin-activated Ca2+-mobilizing (VACM)-1 gene product is a 780-amino acid membrane protein that shares sequence homology with cullins, a family of genes involved in the regulation of cell cycle. However, when expressed in vitro, VACM-1 attenuates basal and vasopressin- and forskolin-induced cAMP production. Mutating the PKA-dependent phosphorylation site in the VACM-1 sequence (S730AVACM-1) prevents this inhibitory effect. To further examine the biological role of VACM-1, we studied the effect of VACM-1 and S730AVACM-1 proteins on cellular proliferation and gene expression in Chinese hamster ovary and COS-1 cells. Cellular proliferation of VACM-1-expressing cell lines was significantly lower compared with that of the vector-transfected cells, whereas it was significantly increased in S730AVACM-1-derived cell lines. Furthermore, expression of VACM-1 but not S730AVACM-1 protein retarded cytokinesis and prevented MAPK phosphorylation. Screening with the Human PathwayFinder-1 GEArray system and subsequent Western blot analysis demonstrated that VACM-1 induces p53 mRNA and protein expression. In summary, VACM-1 inhibits cellular growth by a mechanism that involves cAMP, MAPK phosphorylation, and p53 expression.

Expression of HB-GAM (heparin-binding growth-associated molecules) in the pathways of developing axonal processes in vivo and neurite outgrowth in vitro induced by HB-GAM

1994 ◽  
Vol 79 (2) ◽  
pp. 157-176 ◽  
Author(s):  
Heikki Rauvala ◽  
Anu Vanhala ◽  
Eero Castre´n ◽  
Riitta Nolo ◽  
Erkki Raulo ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Heparin Binding

scholarly journals Recombinant fish neurotrophin-6 is a heparin-binding glycoprotein: implications for a role in axonal guidance

1997 ◽  
Vol 324 (2) ◽  
pp. 461-466 ◽  
Author(s):  
Xiaoling LI ◽  
Juliane FRANZ ◽  
Friedrich LOTTSPEICH ◽  
Rudolf GÖTZ
Keyword(s):  
Neurite Outgrowth ◽  
Recombinant Baculovirus ◽  
Collagen Gel ◽  
Axonal Guidance ◽  
Heparin Binding ◽  
Protease Cleavage ◽  
Binding Glycoprotein ◽  
Collagen Gel Matrix

Neurotrophin-6 (NT-6) was identified in the teleost fish Xiphophorus as a new member of the neurotrophin gene family. NT-6 binds specifically the glycosaminoglycan heparin. In this study NT-6 was expressed in a stably transfected mammalian cell line, and in insect cells via a recombinant baculovirus. It was purified to homogeneity and characterized by MS and N-terminal sequencing. NT-6 from both expression systems was proteolytically processed at one of two protease cleavage motifs and was found to be glycosylated. It supported the survival of embryonic chick sensory neurons; half-maximal survival was observed at 100 ng/ml. Furthermore, NT-6 elicited neurite outgrowth in explanted embryonic dorsal root ganglia. Addition of heparin into the medium did not potentiate the activity of NT-6 in survival assays. However, when a sensory ganglion explant was cultured in a collagen gel matrix assay adjacent to a heparin bead coated with NT-6, neurite outgrowth directed towards the bead was observed. This indicated that NT-6 was slowly released from the heparin bead generating a concentration gradient of NT-6 instrumental for axonal guidance in vitro. Thus the interaction of NT-6 with heparin might not be required for the activation of the cellular receptor for NT-6 on responsive cells but rather may serve to control, in vivo, the distribution of NT-6.

scholarly journals Adherence of pilus- Opa+ gonococci to epithelial cells in vitro involves heparan sulfate.

1995 ◽  
Vol 182 (2) ◽  
pp. 511-517 ◽  
Author(s):  
T Chen ◽  
R J Belland ◽  
J Wilson ◽  
J Swanson
Keyword(s):  
Epithelial Cells ◽  
Heparan Sulfate ◽  
Cho Cells ◽  
Outer Membrane Proteins ◽  
Chinese Hamster ◽  
Heparin Binding ◽  
Low Concentrations ◽  
Strain Ms11 ◽  
High Concentrations

Neisseria gonorrhoeae attaches to host epithelial cells via pili and opacity-associated (Opa) outer membrane proteins. Pilus- gonococci (Gc) of strain MS11 adhere to both human and nonhuman cells, but only when particular Opa proteins are expressed; OpaA+ variants adhere best, OpaC+ variants are next best, and the seven other Opa+ variants adhere poorly or not at all. The adherence of OpaA+ Gc to Chinese hamster ovary (CHO) cells is inhibited by heparin or heparan sulfate (HS), but not by chondroitin sulfate. OpaA+ Gc do not adhere to CHO cells devoid of HS proteoglycans; low concentrations of heparin restore OpaA+ Gc adherence to these HS-deficient CHO cells and high concentrations inhibit it. 3H-heparin binding to whole Gc parallels their adherence abilities (OpaA+ > OpaC+ > OpaH+ > Opas B, D, E, F, G, I = Opa- = 0). Opa proteins separated by SDS-PAGE also bind 3H-heparin. These data suggest that adherence of pilus-, Opa+ Gc involves HS-proteoglycan of eukaryotic cells.

scholarly journals Suppression of tumor formation in vivo by expression of the JE gene in malignant cells.

1991 ◽  
Vol 11 (6) ◽  
pp. 3125-3131 ◽  
Author(s):  
B J Rollins ◽  
M E Sunday
Keyword(s):  
Cho Cells ◽  
Chinese Hamster ◽  
Suppressive Effect ◽  
Tumor Formation ◽  
Host Animal ◽  
Early Growth Response ◽  
Discernible Effect ◽  
Early Growth Response Gene

The early growth response gene JE encodes a monocyte chemoattractant, MCP-1. The JE/MCP-1 protein attracts and stimulates human monocytes and induces monocyte-mediated inhibition of tumor cell growth in vitro. Expression of human or murine JE/MCP-1 in Chinese hamster ovary (CHO) cells completely suppressed their ability to form tumors in nude mice. Coinjection of JE/MCP-1-expressing cells with nonexpressing CHO cells or with HeLa cells also prevented tumor formation. Since JE/MCP-1 expression had no discernible effect on the tranformed phenotype of these cells in vitro, the suppressive effect depends on host animal factors. These factors are likely to be components of the inflammatory response, because JE/MCP-1-expressing cells elicited a predominantly monocytic infiltrate at the site of injection. Our results suggest that JE/MCP-1 protein may be useful in cancer therapy.

scholarly journals A mechanobiological model for tumor spheroids evolution: application to glioblastoma

2021 ◽  
Author(s):  
Ana Carrasco-Mantis ◽  
Hector Castro-Abril ◽  
Teodora Randelovic ◽  
Ignacio Ochoa ◽  
Manuel Doblare ◽  
...  
Keyword(s):  
Cell Line ◽  
Tumor Formation ◽  
Cellular Growth ◽  
Initial Configuration ◽  
Mechanical Activity ◽  
Model Parameters ◽  
Tumor Spheroids ◽  
Cancer Disease ◽  
Hydrogel Matrix

Spheroids are in vitro spherical structures of cell aggregates, eventually cultured within a hydrogel matrix, that are used, among other applications, as a technological platform to investigate tumor formation and evolution. Several interesting features can be replicated using this methodology, such as cell communication mechanisms, the effect of gradients of nutrients, or the creation of realistic 3D biological structures. In this paper, we propose a continuum mechanobiological model which accounts for the most relevant phenomena that take place in tumor spheroids evolution under in vitro suspension, namely, nutrients diffusion in the spheroid, kinetics of cellular growth and death, and mechanical interactions among the cells. The model is qualitatively validated, after calibration of the model parameters, versus in vitro experiments of spheroids of different glioblastoma cell lines. This preliminary validation allowed us to conclude that glioblastoma tumor spheroids evolution is mainly driven by mechanical interactions of the cell aggregate and the dynamical evolution of the cell population. In particular, it is concluded that our model is able to explain quite different setups, such as spheroids growth (up to six times the initial configuration for U-87 MG cell line) or shrinking (almost half of the initial configuration for U-251 MG cell line); as the result of the mechanical interplay of cells driven by cellular evolution. Indeed, the main contribution of this work is to link the spheroid evolution with the mechanical activity of cells, coupled with nutrient consumption and the subsequent cell dynamics. All this information can be used to further investigate mechanistic effects in the evolution of tumors and their role in cancer disease.

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