Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells.

Abstract

BACKGROUND:

Numerous genetic changes are associated with metastasis and invasion of cancer cells. To identify differentially expressed invasion-associated genes, we screened a panel of lung cancer cell lines (CL(1-0), CL(1-1), CL(1-5), and CL(1-5)-F(4) in order of increasing invasive activity) for such genes and selected one gene, collapsin response mediator protein-1 (CRMP-1), to characterize.

METHODS:

We used a microarray containing 9600 gene sequences to assess gene expression in the cell panel and selected the differentially expressed CRMP-1 gene for further study. We confirmed the differential expression of CRMP-1 with northern and western blot analyses. After transfecting and overexpressing CRMP-1 in highly invasive CL(1-5) cells, the cells were assessed morphologically and with an in vitro invasion assay. We used enhanced green fluorescent protein-tagged CRMP-1 and fluorescence microscopy to localize CRMP-1 intracellularly. CRMP-1 expression in 80 lung cancer specimens was determined by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). All statistical tests were two-sided.

RESULTS:

Expression of CRMP-1 was inversely associated with invasive activity in the cell panel, an observation confirmed by northern and western blot analyses. CRMP-1-transfected CL(1-5) cells became rounded and had fewer filopodia and statistically significantly lower in vitro invasive activity than untransfected cells (all P< .001). During interphase, CRMP-1 protein was present uniformly throughout the cytoplasm and sometimes in the nucleus; during mitosis, CRMP-1 was associated with mitotic spindles, centrosomes, and the midbody (in late telophase). Real-time RT-PCR of lung cancer specimens showed that reduced expression of CRMP-1 was statistically significantly associated with advanced disease (stage III or IV; P = .010), lymph node metastasis (N1, N2, and N3; P =.043), early postoperative relapse (P = .030), and shorter survival (P = .016).

CONCLUSIONS:

CRMP-1 appears to be involved in cancer invasion and metastasis and may be an invasion-suppressor gene.

• Authors: J Y Shih, S C Yang, T M Hong, A Yuan, J J Chen, C J Yu, Y L Chang, Y C Lee, K Peck, C W Wu, P C Yang
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 93 Issue 18 Pg. 1392-400 (Sep 19 2001) ISSN: 0027-8874 [Print] United States
• PMID: 11562390 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Neoplasm Proteins
• Nerve Tissue Proteins
• Phosphoproteins
• RNA, Messenger
• RNA, Neoplasm
• Recombinant Fusion Proteins
• collapsin response mediator protein-1

Topics

• Actins (chemistry)
• Adenocarcinoma (genetics, mortality, pathology)
• Aged
• Blotting, Northern
• Blotting, Western
• Carcinoma, Small Cell (genetics, mortality, pathology)
• Cell Cycle (genetics)
• Disease-Free Survival
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Life Tables
• Lung Neoplasms (genetics, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Invasiveness (genetics)
• Neoplasm Metastasis (genetics)
• Neoplasm Proteins (analysis, biosynthesis, genetics, physiology)
• Nerve Tissue Proteins (analysis, biosynthesis, deficiency, genetics, physiology)
• Oligonucleotide Array Sequence Analysis
• Phosphoproteins (analysis, biosynthesis, deficiency, genetics, physiology)
• RNA, Messenger (analysis)
• RNA, Neoplasm (analysis)
• Recombinant Fusion Proteins (analysis)
• Reverse Transcriptase Polymerase Chain Reaction
• Spindle Apparatus (chemistry)
• Subcellular Fractions (chemistry)
• Survival Analysis
• Transfection
• Tumor Cells, Cultured