Maintenance of head and neck tumor gene expression profiles upon lymph node metastasis.
Spread of cancer and development of solid metastases at distant sites is the main cause of cancer-related deaths. To understand and treat metastases, it is important to determine at which stages the most pivotal steps for development of metastases occur. In head and neck squamous cell carcinoma (HNSCC), metastasis nearly always occurs first in local lymph nodes before development of distant metastasis. Here, we have investigated gene expression patterns in HNSCC lymph node metastases using DNA microarrays. Several types of analyses show that the gene expression patterns in lymph node metastases are most similar to the corresponding primary tumors from which they arose, as long as samples contain sufficient proportions of tumor cells. Strikingly, gene expression patterns of metastatic primary HNSCC are largely maintained upon spread to the lymph node. Only a single gene, metastasis-associated gene 1 (MTA1), was found to show consistently changed expression between a large number of matched primary tumor-lymph node metastasis pairs. The maintained expression pattern includes the predictive signature for HNSCC lymph node metastasis. These results underscore the importance of the primary tumor gene expression profile for development and treatment of metastasis. The findings also agree with the concept that disseminated cancer cells alter the surrounding tissue into a metastatic environment that resembles the primary tumor microenvironment.
Roepman
Paul
P
Department of Physiological Chemistry, University Medical Center Utrecht, Utrecht, the Netherlands.
de Jager
Alike
A
Groot Koerkamp
Marian J A
MJ
Kummer
J Alain
JA
Slootweg
Piet J
PJ
Holstege
Frank C P
FC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology*; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012097:Repressor Proteins / Q000235:genetics; D015534:Trans-Activators
C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases