PMID- 17026465
OWN - NLM
STAT- MEDLINE
DCOM- 20070109
LR  - 20061009
IS  - 0001-2815 (Print)
IS  - 0001-2815 (Linking)
VI  - 68
IP  - 4
DP  - 2006 Oct
TI  - Analysis of the expression of HLA class I, proinflammatory cytokines and 
      chemokines in primary tumors from patients with localized and metastatic renal 
      cell carcinoma.
PG  - 303-10
AB  - Changes in the human leukocyte antigen (HLA) class I expression and cytokine and 
      chemokine production both by cancer cells and by normal surrounding tissue are 
      believed to be responsible for immune escape and tumor progression. In this 
      study, we compared the tumor expression levels of HLA heavy chain (HLAhc), 
      beta-2-microglobulin (beta2m), chemokines (Interferon-gamma-inducible Protein-10 
      (IP-10), Interferon-inducible T-cell Alpha-Chemoattractant (I-TAC), Stromal 
      cell-Derived Factor-1 (SDF-1), Macrophage Inflammatory Protein-1-alpha 
      (MIP-1-alpha) and Regulated upon Activation, Normally T-Expressed, and presumably 
      Secreted (RANTES)) and cytokines (Vascular Endothelial Growth Factor (VEGF), 
      Interferon-gamma (IFN-gamma), Interleukin-10 (IL-10), Tumor Growth Factor-beta 
      (TGB-beta)) in primary tumors and adjacent normal tissues from patients with 
      localized and metastatic renal cell carcinoma (RCC) using a quantitative 
      real-time polymerase chain reaction technique. We report that the expression of 
      HLAhc, beta2m and the studied cytokines and chemokines (except for SDF-1) was 
      significantly higher in the tumor (29 samples) than in the normal tissue (14 
      samples). When we compared the tumor expression levels between patients with 
      localized RCC and patients with advanced metastatic stage, we found that the 
      messenger RNA expression levels of HLAhc and beta2m were much lower in patients 
      with metastatic RCC (6 cases) than in patients with localized cancer (23 cases), 
      with levels similar to those in normal tissue. This was also confirmed on a 
      protein level by immunohistological labeling of tumor tissues. Thirty-nine 
      percent of the analyzed RCC tumors showed partial loss of HLA class I molecules, 
      while 6% of the tumors showed HLA class I total loss. The expression of IP-10, 
      SDF-1 and VEGF-c was also significantly lower in patients with advanced tumor, 
      while the IFN-gamma expression in metastatic RCC was not detectable. Our findings 
      show that primary RCC tumors are characterized by a high expression of HLAhc and 
      a presence of proinflammatory mediators and chemokines. We also observed that 
      disease progression and development of metastasis in RCC are associated with 
      decreased expression of HLAhc, beta2m, IP-10, SDF-1 and IFN-gamma. This 
      microenvironment may suppress the cytotoxic response, creating conditions that 
      favor tumor escape and cancer progression.
FAU - Romero, J M
AU  - Romero JM
AD  - Servicio de Analisis Clinicos, Hospital Universitario Virgen de las Nieves, 
      University of Granada, Avenida de las Fuerzas Armadas s/n, 18014 Granada, Spain.
FAU - Aptsiauri, N
AU  - Aptsiauri N
FAU - Vazquez, F
AU  - Vazquez F
FAU - Cozar, J M
AU  - Cozar JM
FAU - Canton, J
AU  - Canton J
FAU - Cabrera, T
AU  - Cabrera T
FAU - Tallada, M
AU  - Tallada M
FAU - Garrido, F
AU  - Garrido F
FAU - Ruiz-Cabello, F
AU  - Ruiz-Cabello F
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Inflammation Mediators)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Renal Cell/chemistry/*immunology/*pathology/secondary
MH  - Chemokines/*analysis/biosynthesis/physiology
MH  - Cytokines/analysis/biosynthesis/physiology
MH  - Female
MH  - Histocompatibility Antigens Class I/*analysis/biosynthesis/physiology
MH  - Humans
MH  - Inflammation Mediators/analysis/*physiology
MH  - Kidney Neoplasms/chemistry/*immunology/*pathology
MH  - Male
MH  - Middle Aged
EDAT- 2006/10/10 09:00
MHDA- 2007/01/11 09:00
CRDT- 2006/10/10 09:00
PHST- 2006/10/10 09:00 [pubmed]
PHST- 2007/01/11 09:00 [medline]
PHST- 2006/10/10 09:00 [entrez]
AID - TAN673 [pii]
AID - 10.1111/j.1399-0039.2006.00673.x [doi]
PST - ppublish
SO  - Tissue Antigens. 2006 Oct;68(4):303-10. doi: 10.1111/j.1399-0039.2006.00673.x.