Article

Gene signatures of pulmonary metastases of renal cell carcinoma reflect the disease-free interval and the number of metastases per patient

Department of Urology, Dresden University of Technology, Dresden, Germany.
International Journal of Cancer (Impact Factor: 5.01). 07/2009; 125(2):474-82. DOI: 10.1002/ijc.24353
Source: PubMed

ABSTRACT Our understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis are largely unknown. Herein, transcriptome-wide expression profiles of a unique cohort of 20 laser-resected pulmonary metastases (Mets) of 18 patients with clear-cell renal cell carcinoma (RCC) were analyzed to identify expression patterns associated with two important prognostic factors in RCC: the disease-free interval (DFI) after nephrectomy and the number of Mets per patient. Differentially expressed genes were identified by comparing early (DFI < or = 9 months) and late (DFI > or = 5 years) Mets, and Mets derived from patients with few (< or =8) and multiple (> or =16) Mets. Early and late Mets could be separated by the expression of genes involved in metastasis-associated processes, such as angiogenesis, cell migration and adhesion (e.g., PECAM1, KDR). Samples from patients with multiple Mets showed an elevated expression of genes associated with cell division and cell cycle (e.g., PBK, BIRC5, PTTG1) which indicates that a high number of Mets might result from an increased growth potential. Minimal sets of genes for the prediction of the DFI and the number of Mets per patient were identified. Microarray results were confirmed by quantitative PCR by including nine further pulmonary Mets of RCC. In summary, we showed that subgroups of Mets are distinguishable based on their expression profiles, which reflect the DFI and the number of Mets of a patient. To what extent the identified molecular factors contribute to the development of these characteristics of metastatic spread needs to be analyzed in further studies.

0 Followers
 · 
81 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The standard treatment choice for cancer metastasis has been systemic management, including cytotoxic chemotherapy, hormonal manipulation, and targeted therapy. Emerging evidence has shown an oligometastatic state, an intermediate state between limited primary cancer and polymetastatic cancer, in which local therapy for metastatic lesions results in satisfactory survival comparable to non-metastatic disease. We provide a comprehensive introduction of evidence from experimental and clinical studies in favor of the oligometastatic phenotype, we review the efficacy and safety of surgery and stereotactic body radiotherapy in the treatment of oligometastases, and finally, we discuss the way to differentiate the oligometastatic state from polymetastasis.
    Radiation Oncology 10/2014; 9(1):230. DOI:10.1186/PREACCEPT-1257312301290358 · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The oligometastatic paradigm implies that patients who develop a small number of metastatic lesions might achieve long-term survival if all these lesions are ablated with surgery or stereotactic radiotherapy. Clinical data indicate that the number of patients with oligometastatic disease receiving aggressive treatment is increasing rapidly. We examine the key evidence supporting or refuting the existence of an oligometastatic state. Numerous single-arm studies suggest that long-term survival is 'better-than-expected' after ablative treatment. However, the few studies with adequate controls raise the possibility that this long-term survival might not be due to the treatments themselves, but rather to the selection of patients based on favourable inclusion criteria. Furthermore, ablative treatments carry a risk of harming healthy tissue, yet the risk-benefit ratio cannot be quantified if the benefits are unmeasured. If the strategy of treating oligometastases is to gain widespread acceptance as routine clinical practice, there should be stronger evidence supporting its efficacy.
    Nature Reviews Clinical Oncology 06/2014; 11(9). DOI:10.1038/nrclinonc.2014.96 · 15.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Increased expression of the tetraspanin TSPAN7 has been observed in a number of cancers; however, it is unclear how TSPAN7 plays a role in cancer progression. We investigated the expression of TSPAN7 in the haematological malignancy multiple myleoma (MM) and assessed the consequences of TSPAN7 expression in the adhesion, migration and growth of MM plasma cells (PC) in vitro and in bone marrow (BM) homing and tumour growth in vivo. Finally, we characterised the association of TSPAN7 with cell surface partner molecules in vitro. TSPAN7 was found to be highly expressed at the RNA and protein level in CD138(+) MM PC from approximately 50% of MM patients. TSPAN7 overexpression in the murine myeloma cell line 5TGM1 significantly reduced tumour burden in 5TGM1/KaLwRij mice 4 weeks after intravenous adminstration of 5TGM1 cells. While TSPAN7 overexpression did not affect cell proliferation in vitro, TSPAN7 increased 5TGM1 cell adhesion to BM stromal cells and transendothelial migration. In addition, TSPAN7 was found to associate with the molecular chaperone calnexin on the cell surface. These results suggest that elevated TSPAN7 may be associated with better outcomes for up to 50% of MM patients. Copyright © 2015. Published by Elsevier Inc.

Full-text (2 Sources)

Download
4 Downloads
Available from
Jan 2, 2015