Heparanase expression at the invasion front of human head and neck cancers and correlation with poor prognosis.
OBJECTIVE
Head and neck squamous cell carcinomas (HNSCC) are characterized by a poor prognosis due to aggressive, recurrent tumor growth. Expression of the extracellular matrix-degrading enzyme heparanase was associated with poorer prognosis in several cancers. We analyzed the presence of heparanase in HNSCC tissues and tumor cells and its potential prognostic significance.


METHODS
We analyzed the expression of the active form of heparanase in HNSCC tissues in corresponding tumor cell cultures and after xenotransplantation of tumor cell cultures into NOD/Scid mice by immunohistochemistry, Western blot analysis, and reverse transcription-PCR in altogether 25 patients and did a comparison with clinicopathologic data of the patients.


RESULTS
Heparanase expression in situ was detected in all tumor biopsies in the tumor stroma and in tumor cells from 13 of 19 primary tumors and 9 of 12 lymph node metastases. Heparanase was localized in disseminated tumor cells, in tumor cell clusters invading adjacent stromal tissues, and in tumor cells at the tumor invasion front. Lymph node metastases expressed higher levels of heparanase compared with corresponding primary tumors. In contrast to a heterogeneous expression pattern in tumor tissues, all corresponding HNSCC tumor cell cultures showed a rather homogeneous heparanase expression on the mRNA and protein levels. Comparison of heparanase expression in situ and in corresponding tumor cell cultures in vitro or after xenotransplantation into NOD/Scid mice revealed that heparanase expression was regulated in vivo. Lack of heparanase in tumor cells from primary tumors or lymph node metastases was correlated with prolonged disease-free survival and overall survival.


CONCLUSIONS
Heparanase expression seems to be involved in the invasiveness and aggressiveness of HNSCC.
Beckhove
Philipp
P
Tumor Immunology Program, German Cancer Research Center, University of Heidelberg, Heidelberg, Germany. P.Beckhove@dkfz.de
Helmke
Burkhard M
BM
Ziouta
Yvonne
Y
Bucur
Mariana
M
Dörner
Wolfgang
W
Mogler
Carolin
C
Dyckhoff
Gerhard
G
Herold-Mende
Christel
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000235:genetics* / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D000099175:Heparanase
D005966:Glucuronidase; D012333:RNA, Messenger; D000099175:Heparanase