PMID- 16096774
OWN - NLM
STAT- MEDLINE
DCOM- 20060308
LR  - 20181113
IS  - 1432-9417 (Print)
IS  - 1432-9417 (Linking)
VI  - 9
IP  - 5
DP  - 2005 Sep
TI  - [Antiangiogenic and anti-immunosuppressive therapeutic strategies in human head 
      and neck squamous cell carcinoma (HNSCC)].
PG  - 273-81
AB  - BACKGROUND: Angiogenesis and tumor-associated immunosuppression are two of the 
      hallmarks of carcinogenesis. In previous studies we demonstrated in vitro that 
      HNSCC tumor cells attract monocytes via monocyte chemotactic protein-1 (MCP-1) 
      and activate them via transforming growth factor-beta 1(TGF-beta1) to secrete 
      interleukin (IL)-1alpha, which in turn stimulates tumor cells to secrete 
      increased levels of the angiogenic and immunosuppressive vascular endothelial 
      growth factor (VEGF). These findings suggest that interaction between the immune 
      system and VEGF-mediated angiogenesis is important for progression of HNSCC. 
      Recent studies in vitro show that retinoic acid (RA) downregulates the release of 
      MCP-1 and TGF-beta1 by tumor cells. Therefore, we investigated the ability of RA 
      to modulate the ability of tumor cells to recruit and activate monocytes for 
      participation in VEGF-mediated angiogenesis and immunosuppression in vivo. 
      MATERIAL AND METHODS: Mice (ten/group) were injected daily with RA (160 
      microg/kg) for 3 weeks. After that time mice were sacrificed, and paraffin 
      sections of tumors were obtained and stained for VEGF-A, CD68, and PECAM (CD31) 
      by immunohistochemistry. The lungs, liver, and myocardium were analyzed for 
      macro- and micrometastases. The plasma protein levels of VEGF-A and MCP-1 were 
      determined by ELISA. RESULTS: In RA-treated mice tumors regressed completely and 
      RA prevented metastases (p=0.00) and macrophage infiltration (p=0.007). Treated 
      mice downregulated VEGF-A (0 pg/ml) and MCP-1 (12 pg/ml) in peripheral blood 
      (p=0.001). CONCLUSION: Our findings suggest a new therapeutic possibility: the 
      development of treatment protocols that can block each of the ways in which 
      tumors induce new blood vessel growth and immunosuppression of the host.
FAU - Strauss, L
AU  - Strauss L
AD  - Abteilung Onkologie, Universitatsspital Zurich. strauss_ewers@hotmail.com
FAU - Volland, D
AU  - Volland D
FAU - Guerrero, A
AU  - Guerrero A
FAU - Reichert, T
AU  - Reichert T
LA  - ger
PT  - English Abstract
PT  - Journal Article
TT  - Tumorangiogenese und Immunsuppression. Strategische Angriffspunkte fur neue 
      Therapieansatze beim Plattenepithelkarzinom der Mundhohle (HNSCC).
PL  - Germany
TA  - Mund Kiefer Gesichtschir
JT  - Mund-, Kiefer- und Gesichtschirurgie : MKG
JID - 9716576
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Animals
MH  - Carcinoma, Squamous Cell/*blood supply/*immunology
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/antagonists & inhibitors/physiology
MH  - Disease Progression
MH  - Down-Regulation/drug effects
MH  - Humans
MH  - Immune Tolerance/*drug effects
MH  - Interleukin-1/metabolism
MH  - Macrophage Activation/*drug effects/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred A
MH  - Mouth Neoplasms/*blood supply/*immunology
MH  - Neoplasm Metastasis
MH  - Neoplasm Transplantation
MH  - Transforming Growth Factor beta/antagonists & inhibitors/physiology
MH  - Transforming Growth Factor beta1
MH  - Tretinoin/*pharmacology
MH  - Vascular Endothelial Growth Factor A/physiology
EDAT- 2005/08/13 09:00
MHDA- 2006/03/09 09:00
CRDT- 2005/08/13 09:00
PHST- 2005/08/13 09:00 [pubmed]
PHST- 2006/03/09 09:00 [medline]
PHST- 2005/08/13 09:00 [entrez]
AID - 10.1007/s10006-005-0635-3 [doi]
PST - ppublish
SO  - Mund Kiefer Gesichtschir. 2005 Sep;9(5):273-81. doi: 10.1007/s10006-005-0635-3.