Tropism between hepatic and pulmonary metastases in colorectal cancers.
In metastatic colorectal cancers, tumor cells are disseminated prior to             surgical resection of the primary tumor but remain dormant until proper colonization             mechanisms are activated. To identify the colonization mechanisms of the metastatic             tumors, we conducted a pairwise comparison between primary colorectal cancers             and metastatic tumors (n=12 pairs), including six hepatic pairs and six pulmonary             pairs. The mRNA levels of 224 genes previously reported to be associated with             metastasis, cytokines and angiogenesis were quantitatively determined by PCR arrays.             Among them, 27 genes were duplicated or triplicated to show consistent expression.             Unsupervised hierarchical clustering of the Ct values of metastasis-related genes             revealed that liver metastases were indistinguishable from primary colorectal             cancers (n=5/6), whereas lung metastases were highly diversified from one another             and from the primary tumors (n=6/6). Cytokines and receptor gene expression array             data also confirmed the divergence of pulmonary metastases from primary colorectal             cancers (n=6/6). Heat map analyses of ΔCt values of the metastasis-related genes             identified a 17-gene tropism signature that was sufficient not only to distinguish             liver and the lung metastases, but also reconstituted the clustering of primary             tumors with the hepatic metastases (n=17/18). In this pilot experiment, pulmonary             metastases were significantly diverged from hepatic metastases that were indistinguishable             from primary colorectal cancers. Further genomic and clinical studies are in progress             to evaluate the potential of the tropism signature as a therapeutic target to             inhibit the colonization of metastatic colorectal cancers.
Samsung Biomedical Research Institute, Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul 135-710, Republic of Korea.
Sung-Hyun
SH
Kim
So-Jung
SJ
Choi
Joon Suk
JS
Park
Jinseon
J
Lee
Yong Beom
YB
Cho
Min-Woong
MW
Kang
Woo Yong
WY
Lee
Yong Soo
YS
Choi
Hong Kwan
HK
Kim
Joungho
J
Han
Ho-Kyung
HK
Chun
Jhingook
J
Kim
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018523:Tropism / Q000235:genetics*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger