A study of the heterogeneity of the mucoepidermoid tumor and the implication for future therapies.
Mucoepidermoid carcinomas are common head and neck neoplasms whose wide distribution includes the major salivary glands, especially parotid, the minor salivary glands within the oropharynx, sites within the larynx, and the submucosal bronchial glands. These tumors are heterogeneous neoplasms composed of intermediate, squamous, and mucous cell subpopulations and have been traditionally classified as low or high grade based on their histological nature and tendency for invasion and metastasis. To gain a better understanding of the heterogeneity of these tumors, we conducted in-depth studies of the different cellular subpopulations obtained from primary human mucoepidermoid carcinomas from various sites, and a derived cell line grown in monolayer culture and as a nude mouse xenograft. Flow cytometric and clonal dilution studies indicate that the intermediate cell behaves as a reserve cell capable of differentiating into either the squamous cell or mucous cell. Immunocytochemical studies of bromodeoxyuridine uptake and Ki-67 antigen expression indicate that whereas the squamous and mucous cells are terminally differentiated and permanently arrested in G0, the intermediate cell actively enters G1 and S. Studies of invasion utilizing a human amnionic membrane indicate that only the intermediate cell is capable of active invasion. Because the mucous and squamous cells are incapable of further division or invasion, therapeutic strategies aimed at differentiating the intermediate cell in vivo into either mucous or squamous directions would serve as useful adjuncts to surgery by reducing the rate of recurrence and the incidence of metastasis.
Ross
D A
DA
Division of Head and Neck Surgery, UCLA School of Medicine 90024.
Huaman
J A
JA
Barsky
S H
SH
D000818:Animals; D002277:Carcinoma / Q000473:pathology* / Q000628:therapy; D002455:Cell Division; D002469:Cell Separation; D002471:Cell Transformation, Neoplastic; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010641:Phenotype; D014407:Tumor Cells, Cultured