The Angiogenic Switch Molecule, Secreted FGF-Binding Protein, an Indicator of Early Stages of Pancreatic and Colorectal Adenocarcinoma

Abstract

Tumor angiogenesis has been related to the initiation as well as progression toward more aggressive behavior of human tumors. We will discuss genetic events underlying the initiation and progression of colorectal and pancreatic adenocarcinoma with a particular focus on the modulation of angiogenesis. A secreted fibroblast growth factor (FGF) binding protein (FGF-BP), which is an extracellular chaperone molecule for FGFs, has been shown to enhance FGF-mediated biochemical and biologic events and to be a crucial rate-limiting factor for tumor-dependent angiogenesis. Histochemical and in situ hybridization studies with archival samples show that FGF-BP is induced early during the initiation of colorectal and pancreatic adenocarcinoma. We will discuss the potential of this secreted protein as a serum marker to identify at-risk subjects.

Role of fibroblast growth factors in pancreatic cancer

“…Активация ангиогенного переключения, эффекта, при котором суммарное влияние ангиогенных активаторов (VEGF, FGF, TNFa, MMP) перевешивает действие ингибиторов ангиогенеза (TIMP, IL-4, IFNa, Ang2), на ранних стадиях развития опухоли чаще всего ограничивает переход от небольшой патологии к серьезному заболеванию. И хотя рак поджелудочной железы не относится к опухолям с большим количеством кровеносных сосудов, одной из его особенностей является значительное усиление опухоль-зависимого неоангиогенеза [50,51].…”

A Novel Enhancer of the Wound Healing Process

“…7 The observed increased expression of FGF-BPs at early stages of the development of pancreatic and colorectal adenocarcinomas suggested that they could be used as a diagnostic screening method for detection of premalignant cancers, provided that they are released into the circulation of these patients. 9 Most importantly, at least FGF-BP1 seems to play a functional role in tumorigenesis. Thus, it was shown in xenograft models for human cervical squamous cell carcinoma and colon adenocarcinoma that ribozyme-mediated suppression of FGF-BP expression inhibits angiogenesis-dependent tumor growth.…”

Dérèglements cellulaires et moléculaires à l’origine du phénotype métastatique

“…L'altération du 4p est associée de manière récurrente à un mauvais pronostic [11,12]. Nos résultats suggèrent qu'une inactivation par bi-mutation ponctuelles favoriserait l'acquisition du pouvoir métastatique.…”

“…Nos résultats suggèrent qu'une inactivation par bi-mutation ponctuelles favoriserait l'acquisition du pouvoir métastatique. Le gène de la FGF-binding protein, localisé en 4p11, et de mauvais pronostic dans les cancers coliques et pancréatiques, pourrait être le gène impliqué [12]. Sa mutation très précoce surviendrait juste après celle d'APC et modifierait la disponibilité des protéines de la famille FGF dont le gradient morphogénique régule la différenciation et la polarisation cellulaires [3].…”