Protection of thyroid cancer cells by complement-regulatory factors.
BACKGROUND
Clinical and experimental studies have suggested that complement activation may play a role in tumor cytotoxicity. Little information is available concerning the presence of complement activation and the localization of complement-regulatory factors in cells or tissues of malignant tumors. The aim of the present study was to examine, using immunohistochemistry and immunoelectron microscopy, whether the complement system is activated in tissues of thyroid carcinoma and whether thyroid carcinoma cells are protected from cell lysis by in situ complement activation.


METHODS
Fresh tissues were obtained by thyroidectomy from 15 patients with papillary carcinomas, 7 with follicular carcinomas, and 5 with follicular adenomas. In addition, five specimens of histologically normal thyroid tissue and five specimens of chronically inflamed tissue adjacent to thyroid neoplasms were studied. Immunohistochemical and immunoelectron microscopic localization of complement components, C3d and C5b-9, and the complement-regulatory factors, such as s-protein, decay-accelerating factor (CD55), membrane cofactor protein (CD46), complement receptor types 1 (CD35) and 2 (CD21), and protectin (CD59), were examined in these tissues.


RESULTS
The staining patterns of C3d, C5b-9, and s-protein were positive and homogeneous in the nonneoplastic and most neoplastic thyroid tissues. Immunoelectron microscopy showed these antigens were localized mainly on the subepithelial and vascular basement membranes and attached to the cell surface of thyroid follicular cells. Decay-accelerating factor (CD55) was present homogeneously on the basement membranes, on the basal cell border of the thyroid follicular cells, and often on the luminal surface of carcinoma cells. Both membrane cofactor protein (CD46) and protectin (CD59) were expressed strongly on the cell surface of almost all benign and malignant thyroid follicular cells. Membrane cofactor protein was expressed on both the basal and lateral membrane, showing cell-to-cell interaction, but rarely on the luminal surface, whereas protectin was expressed strongly on the luminal surface and often on the basal cell border but rarely on the lateral membrane. Neither complement receptor type 1 (CD35) nor complement receptor type 2 (CD21) was expressed on any thyroid follicular cells.


CONCLUSIONS
The present study confirmed the presence of complement activation with subsequent deposition of C3d and C5b-9 complexes in thyroid carcinomas. It also indicated that thyroid carcinoma cells are protected from cell lysis because of complement activation in multiple phases by complete coverage of the entire cell membrane surface with complement-regulatory factors. These findings were similar to those found in nonneoplastic thyroid follicular cells.
Yamakawa
M
M
Second Department of Pathology, Yamagata University School of Medicine, Japan.
Yamada
K
K
Tsuge
T
T
Ohrui
H
H
Ogata
T
T
Dobashi
M
M
Imai
Y
Y
D000236:Adenoma / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D018958:CD55 Antigens; D018957:CD59 Antigens; D003167:Complement Activation / Q000276:immunology*; D015933:Complement C3d / Q000032:analysis; D015938:Complement Membrane Attack Complex / Q000032:analysis; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis; D017464:Receptors, Complement 3d / Q000032:analysis; D013961:Thyroid Gland / Q000276:immunology; D013964:Thyroid Neoplasms / Q000276:immunology*; D019096:Vitronectin
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D017464:Receptors, Complement 3d; D019096:Vitronectin; D015933:Complement C3d