ABSTRACT
Metastasis is a multistep and multifunctional biological cascade that is the final and most life-threatening stage of cancer progression. Understanding the biological underpinnings of this complex process is of extreme clinical relevance and requires unbiased and comprehensive biological scrutiny. In recent years, we have utilized a xenograft model of breast cancer metastasis to discover genes that mediate organ-specific patterns of metastatic colonization. Examination of transcriptomic data from cohorts of primary breast cancers revealed a subset of site-specific metastasis genes that are selected for early in tumor progression. High expression of these genes predicts the propensity for lung metastasis independently of several classic markers of poor prognosis. These genes fulfill dual functions-enhanced primary tumorigenicity and augmented organ-specific metastatic activity. Other metastasis genes fulfill functions specialized for the microenvironment of the metastatic site and are consequently not selected for in primary tumors. These findings improve our understanding of metastatic progression, facilitate the interpretation of primary tumor gene expression data, and open several important possibilities for future clinical application.
Subject(s)
Neoplasm Metastasis/genetics , Oncogenes , Animals , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Bone Neoplasms/secondary , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , Female , Gene Expression Profiling , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Mice , Neoplasm Metastasis/pathology , Neoplasm Transplantation , Organ Specificity , Prognosis , Transplantation, HeterologousABSTRACT
The protein compositions of archaebacteria (Halobacterium salinarium, Halobacterium volcanii, Halobacterium saccharovorum and Natronobacterium pharaonis 12) flagella have been studied. It was found that flagella of these archaebacterial species are made up of flagellins. The flagellins of H. salinarium, H. volcanii and H. saccharovorum are glycosylated. Based on the known primary sequences of Halobacterium halobium R1M1 flagellin genes, oligonucleotides to the 5'- and 3'-ends of locus A containing two out of five such genes have been synthesized. The amplified by primers fragment of chromosomal DNA coding for H. halobium flagellins A1 and A2 was used as a probe for detecting homologous sites in archaebacterial DNA. Southern blotting hybridization revealed that the DNA of all archaebacterial species tested in this study contains sequences that are homologous to genes flg A1 and flg A2 of H. halobium.