92-kd gelatinase is actively expressed by eosinophils and stored by neutrophils in squamous cell carcinoma.
Tumor invasion and metastasis are assisted by multiple proteinases that degrade basement membrane and stromal matrix components. We used in situ hybridization with 35S-labeled RNA probes and immunohistochemistry to localize cellular sites of 92-kd gelatinase production in sections of invasive squamous cell carcinoma. Signal for enzyme messenger RNA was detected only in numerous eosinophils that surrounded the tumor nodules, and immunohistochemical staining verified the presence of enzyme protein in these granulocytes and also revealed strong reactivity in neutrophils. No resident or other migratory cell type was positive for gelatinase messenger RNA or protein, and no signal was detected by either assay in samples of healthy skin. These data indicate that eosinophils have the capacity to synthesize actively 92-kd gelatinase, whereas neutrophils store and probably release the enzyme on demand. Because of the capacity of 92-kd gelatinase to degrade both basement membrane and interstitial extracellular matrix molecules, the expression, delivery, and secretion of this metalloproteinase by granulocytes may be critical for tumor invasion.
Ståhle-Bäckdahl
M
M
Department of Dermatology, Karolinska Hospital, Stockholm, Sweden.
Parks
W C
WC
D001345:Autoradiography; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D004804:Eosinophils / Q000201:enzymology*; D018093:Gelatinases; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D008970:Molecular Weight; D009361:Neoplasm Invasiveness; D009504:Neutrophils / Q000201:enzymology*; D010434:Pepsin A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013194:Staining and Labeling
D012333:RNA, Messenger; D010434:Pepsin A; D018093:Gelatinases