Therapeutic Targeting of Tumor Growth and Angiogenesis with a Novel Anti-S100A4 Monoclonal Antibody

نویسندگان

  • Jose Luis Hernández
  • Laura Padilla
  • Sheila Dakhel
  • Toni Coll
  • Rosa Hervas
  • Jaume Adan
  • Marc Masa
  • Francesc Mitjans
  • Josep Maria Martinez
  • Silvia Coma
  • Laura Rodríguez
  • Véronique Noé
  • Carlos J. Ciudad
  • Francesc Blasco
  • Ramon Messeguer
چکیده

S100A4, a member of the S100 calcium-binding protein family secreted by tumor and stromal cells, supports tumorigenesis by stimulating angiogenesis. We demonstrated that S100A4 synergizes with vascular endothelial growth factor (VEGF), via the RAGE receptor, in promoting endothelial cell migration by increasing KDR expression and MMP-9 activity. In vivo overexpression of S100A4 led to a significant increase in tumor growth and vascularization in a human melanoma xenograft M21 model. Conversely, when silencing S100A4 by shRNA technology, a dramatic decrease in tumor development of the pancreatic MiaPACA-2 cell line was observed. Based on these results we developed 5C3, a neutralizing monoclonal antibody against S100A4. This antibody abolished endothelial cell migration, tumor growth and angiogenesis in immunodeficient mouse xenograft models of MiaPACA-2 and M21-S100A4 cells. It is concluded that extracellular S100A4 inhibition is an attractive approach for the treatment of human cancer.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

In vitro combination therapy of pathologic angiogenesis using anti-vascular endothelial growth factor and anti-neuropilin-1 nanobodies

Objective(s): Emergence of resistant tumor cells to the current therapeutics is the main hindrance in cancer treatment. Combination therapy, which mixes two or more drugs, is a way to overcome resistant problems of cancer cells to current treatments.  Nanobodies are promising tools in cancer therapy due to their high affinity as well as high penetration to tumor sites....

متن کامل

Inhibition of VEGF‐dependent angiogenesis and tumor angiogenesis by an optimized antibody targeting CLEC14a

The C-type lectin-like domain of CLEC14a (CLEC14a-C-type lectin-like domain [CTLD]) is a key domain that mediates endothelial cell-cell contacts in angiogenesis. However, the role of CLEC14a-CTLD in pathological angiogenesis has not yet been clearly elucidated. In this study, through complementarity-determining region grafting, consecutive deglycosylation, and functional isolation, we generated...

متن کامل

In vivo immunotherapy of lung cancer using cross-species reactive vascular endothelial growth factor nanobodies

Objective(s): Lung cancer is the main leading cause of cancer death worldwide. Angiogenesis is the main step in proliferation and spreading of tumor cells. Targeting vascular endothelial growth factor (VEGF) is an effective approach for inhibition of cancer angiogenesis. Nanobodies (NBs) are a novel class of antibodies derived from the camel. Unique characteristics of Nbs like their small size ...

متن کامل

MT95-4, a fully humanized antibody raised against aminopeptidase N, reduces tumor progression in a mouse model

Aminopeptidase N (APN/CD13) is involved in tumor cell invasion and tumor angiogenesis and is considered a promising therapeutic target in the treatment of cancer. To develop a novel monoclonal antibody-based cancer therapy targeting APN/CD13, we established a fully humanized anti-APN/CD13 monoclonal antibody, MT95-4. In vitro, MT95-4 inhibited APN/CD13 enzymatic activity on the tumor cell surfa...

متن کامل

GPI-Anchored Fibromodulin as a Novel Target in Chronic Lymphocytic Leukemia: Diagnostic and Therapeutic Implications

Background: We have previously reported the aberrant expression of Fibromodulin (FMOD) in patients with chronic lymphocytic leukemia (CLL). Although FMOD has been considered as a cytoplasmic or secretory protein, we discovered the cell surface expression of FMOD in leukemic B cells via anchoring with glycosylphosphatidylinositol (GPI). Objective: To evaluate FM...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2013