RGD Reference Report - Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients. - Rat Genome Database

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Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients.

Authors: Hilfenhaus, Georg  Göhrig, Andreas  Pape, Ulrich-Frank  Neumann, Tabea  Jann, Henning  Zdunek, Dietmar  Hess, Georg  Stassen, Jean Marie  Wiedenmann, Bertram  Detjen, Katharina  Pavel, Marianne  Fischer, Christian 
Citation: Hilfenhaus G, etal., Endocr Relat Cancer. 2013 May 20;20(3):305-19. doi: 10.1530/ERC-12-0223. Print 2013 Jun.
RGD ID: 14349029
Pubmed: PMID:23463017   (View Abstract at PubMed)
DOI: DOI:10.1530/ERC-12-0223   (Journal Full-text)

Placental growth factor (PlGF), a VEGF-homolog implicated in tumor angiogenesis and adaptation to antiangiogenic therapy, is emerging as candidate target in malignancies. Here, we addressed the expression, function, and prognostic value of PlGF in neuroendocrine tumors (NETs). PlGF was determined in NET patients' sera collected retrospectively (n=88) and prospectively (n=87) using Roche-Elecsys and correlated with clinicopathological data. Tumoral PlGF was evaluated by immunohistochemistry, effects of PlGF on proliferation and migration in vitro were assessed using different NET cell lines and effects on tumor growth in vivo in orthotopic xenografts. Circulating and tumoral PlGF was elevated in patients with pancreatic NETs (pNETs) compared with control sera and respective healthy tissue. De novo PlGF expression occurred primarily in the tumor stroma, suggesting paracrine stimulatory circuits. Indeed, PlGF enhanced NET proliferation and migration in vitro and, conversely, neutralizing antibodies to PlGF reduced tumor growth in vivo. Elevated circulating PlGF levels in NET patients correlated with advanced tumor grading and were associated with reduced tumor-related survival in pNETs. Subsequent determinations confirmed and extended our observation of elevated PlGF levels in a prospective cohort of grade 1 and grade 2 pNETs (n=30) and intestinal NETs (n=57). In low-grade pNETs, normal circulating PlGF levels were associated with better survival. In intestinal NETs, circulating PlGF above median emerged as an independent prognostic factor for shorter time-to-progression in multivariate analyses. These data assign to PlGF a novel function in the pathobiology of NETs and propose PlGF as a prognostic parameter and therapeutic target.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PGFHumanpancreatic endocrine carcinoma disease_progressionIEP protein:increased expression:serum (human)RGD 
PgfRatpancreatic endocrine carcinoma disease_progressionISOPGF (Homo sapiens)protein:increased expression:serum (human)RGD 
PgfMousepancreatic endocrine carcinoma disease_progressionISOPGF (Homo sapiens)protein:increased expression:serum (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pgf  (placental growth factor)

Genes (Mus musculus)
Pgf  (placental growth factor)

Genes (Homo sapiens)
PGF  (placental growth factor)


Additional Information