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HCT116 PCLKC

ABSTRACT: The gain of Protocadherin LKC (PCDH24) expression in colon carcinoma cell line HCT116 has been shown to induce contact inhibition, thereby completely abolishing tumor formation in vivo. To clarify the molecular mechanism, we performed DNA microarray analysis and compared gene-expression pattern between control and PCDH24-expressing HCT116 cells. Approximately 2000 genes were apparently changed their expression. Further proteomics analysis using 2-DE/MS confirmed the dramatic changes and provided additional information. We were aware that these changes are quite similar to the changes observed in epithelial-mesenchymal transition (EMT), most drastic changes in development and cancer metastasis. We thus further analyzed these changes using specific antibodies, and found distinct difference between these two phenomena. Among the differences, nuclear translocation of catenin beta 1 (CTNNB1) was inhibited by PCDH24-expression, subsequently some of the downstream nodes were suppressed. Although contact inhibition and cancer metastasis are completely opposite aspect of the cells, we expect that the identified differences will be key nodes to understand the relationship. We also expect that the nodes will be a target to modulate tumors arising stem cell transplantation (SCT), as well as a therapeutic target for cancer metastasis. Keywords: dose response

ORGANISM(S): Homo sapiens

PROVIDER: GSE10650 | GEO | 2009/02/26

SECONDARY ACCESSION(S): PRJNA107733

REPOSITORIES: GEO

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Project description:Lymph node metastasis is a poor prognosis indicator in esophageal cancer. Although tumor spreading currently forms the main basis for therapy selection, the molecular mechanisms underlying the metastatic pathway remain insufficiently understood. Several studies aimed to investigate these mechanisms but focused mainly on regulatory patterns in the tumors themselves and/or the invaded lymph nodes. To date no study has yet investigated the potential changes on transcription level, which take place within the yet non-invaded niche. Here we provide a comprehensive description of these regulations in patients. In this study the transcriptomic profiles of regional lymph nodes were determined for two patient groups: patients classified as pN1 (metastasis) or pN0 (no metastasis) respectively. All investigated lymph nodes, also those from pN1 patients, were still free of metastasis. The gene expression data was obtained via microarray analysis. Top candidates were validated via PCR and immunohistochemistry. The results show that regional lymph nodes of pN1 patients differ decisively from those of pN0 patients – even before metastasis has taken place. In the pN0 group distinct immune response patterns were observed. In contrast, lymph nodes of the pN1 group exhibited a clear profile of reduced immune response and reduced proliferation, but increased apoptosis, enhanced hypoplasia and morphological conversion processes. DKK1 was the most significant gene associated with the molecular mechanisms taking place in lymph nodes of patients suffering from metastasis (pN1). We assume that the two molecular profiles observed constitute two different stages of a progressive disease. Finally we suggest that DKK1 might play an important role within the mechanisms leading to lymph node metastasis. First, samples were classified according to the principal status of the patients exhibiting (pN1 group) or non-exhibiting (pN0 group) metastasis in regional lymph nodes. The comparison of pN1 and pN0 patients should highlight the general differences in regulations that might lead to or prevent from metastasis. Second, two lymph node samples were collected from each patient, one node located close to the tumor (regional) and the second node distant to the tumor. While the distant nodes served as reference sample the regional nodes were investigated for transcriptional regulations. Key to the work presented here is that all nodes investigated were made sure to be still metastasis free, independent of the patients’ pN1/pN0 classification and of the location relative to the tumor. This should allow the identification of early changes occurring prior to metastasis homing.

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HCT116 PCLKC

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