Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1.
Multipotent stromal cells (MSCs) have been shown to reduce apoptosis in injured cells by secretion of paracrine factors, but these factors were not fully defined. We observed that coculture of MSCs with previously UV-irradiated fibroblasts reduced apoptosis of the irradiated cells, but fresh MSC conditioned medium was unable reproduce the effect. Comparative microarray analysis of MSCs grown in the presence or absence of UV-irradiated fibroblasts demonstrated that the MSCs were activated by the apoptotic cells to increase synthesis and secretion of stanniocalcin-1 (STC-1), a peptide hormone that modulates mineral metabolism and has pleiotrophic effects that have not been fully characterized. We showed that STC-1 was required but not sufficient for reduction of apoptosis of UV-irradiated fibroblasts. In contrast, we demonstrated that MSC-derived STC-1 was both required and sufficient for reduction of apoptosis of lung cancer epithelial cells made apoptotic by incubation at low pH in hypoxia. Our data demonstrate that STC-1 mediates the antiapoptotic effects of MSCs in two distinct models of apoptosis in vitro.
Block
Gregory J
GJ
Tulane Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA, 70112.
Ohkouchi
Shinya
S
Tulane Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA, 70112.
Fung
France
F
Tulane Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA, 70112.
Frenkel
Joshua
J
Tulane Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA, 70112.
Gregory
Carl
C
Tulane Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA, 70112.
Pochampally
Radhika
R
Tulane Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA, 70112.
DiMattia
Gabriel
G
London Regional Cancer Program and the Dept. of Oncology, Biochemistry, The University of Western Ontario.
Sullivan
Deborah E
DE
Tulane University, Department of Microbiology and Immunology, New Orleans LA, 70112.
Prockop
Darwin J
DJ
Tulane Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA, 70112.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D006023:Glycoproteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014162:Transfection; D014466:Ultraviolet Rays; D015854:Up-Regulation
D017077:Culture Media, Conditioned; D006023:Glycoproteins; C051795:teleocalcin