The isolation of novel mesenchymal stromal cell chemotactic factors from the conditioned medium of tumor cells.
Bone marrow-derived mesenchymal stromal cells (MSCs) localize to solid tumors. Defining the signaling mechanisms that regulate this process is important in understanding the role of MSCs in tumor growth. Using a combination of chromatography and electrospray tandem mass spectrometry we have identified novel soluble signaling molecules that induce MSC chemotaxis present in conditioned medium of the breast carcinoma cell line MDA-MB231. Previous work has employed survey strategies using ELISA assay to identify known chemokines that promote MSC chemotaxis. While these studies provide valuable insights into the intercellular signals that impact MSC behavior, many less well-described, but potentially important soluble signaling molecules could be overlooked using these methods. Through the less directed method of column chromatography we have identified novel candidate MSC chemotactic peptides. Two proteins, cyclophilin B and hepatoma-derived growth factor were then further characterized and shown to promote MSC chemotaxis.
Lin
Siang-Yo
SY
Department of Pharmacology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA.
Yang
Jun
J
Everett
Allen D
AD
Clevenger
Charles V
CV
Koneru
Mythili
M
Mishra
Pravin J
PJ
Kamen
Barton
B
Banerjee
Debabrata
D
Glod
John
J
D000595:Amino Acid Sequence; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D001943:Breast Neoplasms; D002630:Chemotactic Factors / Q000737:chemistry* / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology; D002846:Chromatography, Affinity / Q000379:methods; D017077:Culture Media, Conditioned / Q000737:chemistry*; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000378:metabolism*
D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011994:Recombinant Proteins; C051610:hepatoma-derived growth factor; C081786:cyclophilin B; D021983:Cyclophilins