Expression of galectin-3-reactive ligands in squamous cancer and normal epithelial cells as a marker of differentiation.
The definition of biological markers for oropharynx and larynx cancer is essential to predict their clinical behavior. Since cellular glycans play an important role in biological information transfer, we have employed an endogenous lectin, galectin-3, to examine in primary squamous carcinomas, lymph node metastases, and physiological squamous epithelia whether glycans recognized by this lectin are altered in relation to the state of differentiation. The expression of galectin-3 was concomitantly evaluated by immunohistochemistry using the A1D6 monoclonal antibody. In addition, other antibodies were used for the detection of cytokeratins and desmosomal proteins (desmoplakin-1 and desmoglein). The results show the expression of galectin-3-reactive ligands in moderately/highly differentiated carcinomas only in areas exhibiting a high level of keratinization. Except for one patient out of 14, metastatic cells in lymph nodes expressed no accessible binding sites for galectin-3. No galectin-3-reactivity was detected in the basal cell layer of all studied normal epithelia (which contains the proliferating cells). The suprabasal layers were positive in epidermis and epithelium of tongue and cornea and negative in epithelium of palatine tonsil. The tumor cells expressed galectin-3 with an intensity positively correlated with tumor differentiation. The position of galectin-3-reactive sites colocalized with the two tested desmosomal proteins. However, presence of these proteins was also detected in areas of tumor and suprabasal layers of tonsil epithelium where no binding reactivity for galectin-3 was found. The present study showed that expression of galectin-3-reactive glycoligands is differentiation-dependent in normal as well as malignant squamous cells. Colocalization of galectin-3-reactive sites with desmosomal proteins (desmoplakin-1 and desmoglein) suggests an association of the galectin-3 ligand(s) with the cell surface, pointing to a potential participation of galectin-3 in mediation of intercellular contacts in these tumor types.
Plzák
J
J
Institute of Anatomy, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Smetana
K
K
Hrdlicková
E
E
Kodet
R
R
Holíková
Z
Z
Liu
F T
FT
Dvoránkova
B
B
Kaltner
H
H
Betka
J
J
Gabius
H J
HJ
D000943:Antigens, Differentiation / Q000378:metabolism*; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051182:Desmogleins; D051180:Desmoplakins; D004847:Epithelial Cells / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D037502:Galectin 3; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008024:Ligands; D008207:Lymphatic Metastasis / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis
D000943:Antigens, Differentiation; D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; C495294:DSP protein, human; D051182:Desmogleins; D051180:Desmoplakins; D005456:Fluorescent Dyes; D037502:Galectin 3; D008024:Ligands; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D007633:Keratins