The origin of hyaluronectin in human tumors.
The origin of tumor stroma hyaluronectin (HN), a glycoprotein that binds to hyaluronan (HA), has long remained unknown. Histological observations of human tumors suggest that tumor HN could originate from stroma fibroblasts, and in some cases from inflammatory cells. The fibroblast origin was confirmed by the discovery of HN-like antigen along with hyaluronan in culture medium of tumor-derived fibroblasts. An HA-binding protein was characterized in the culture medium of peripheral blood mononuclear cells (PBMC) in both normal subjects and tumor-bearing patients and was found to be human HN. Cultivated monocytes did not produce HA. HN was not related to the HA-binding site CD44. Sequencing of brain HN-derived peptides demonstrated that each determined peptide sequence was similar to a sequence of the proteoglycan PG-M/versican, suggesting that HN is the HA-binding moiety of the proteoglycan. One probe was synthesized from human PBMC by polymerase chain reaction with primers derived from HN sequences also found in versican. Northern blots were positive only with HN-producing cells. The main RNAs were in the 6-8 kb range, and there was a limited proportion of smaller RNA, which was compatible with the size expected from the HN molecular mass. Southern blotting of monocytes and tumor cells demonstrated that the gene was limited to a unique band. We conclude that HN, an extracellular component of brain, connective embryonic, inflammatory and tumoral tissues, is a PG-M/versican-derived molecule. Our results suggest that tumor HN, which originates from fibroblasts and monocytes of tumor stroma, is a molecular component of the host-tumor relationship and could play a role in the regulation of HA activity in oncogenesis.
Delpech
B
B
Laboratoire d'Oncologie Moléculaire, Centre Henri-Becquerel, Rouen, France.
Girard
N
N
Olivier
A
A
Maingonnat
C
C
van Driessche
G
G
van Beeumen
J
J
Bertrand
P
P
Duval
C
C
Delpech
A
A
Bourguignon
J
J
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D018076:DNA, Complementary; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D002352:Carrier Proteins; D018076:DNA, Complementary; D006023:Glycoproteins; D010446:Peptide Fragments; C108676:hyaluronectin protein, human; D006820:Hyaluronic Acid; D003094:Collagen