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2018 ; 37
(19
): 2573-2585
Nephropedia Template TP
gab.com Text
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English Wikipedia
Alternative transcription of a shorter, non-anti-angiogenic thrombospondin-2
variant in cancer-associated blood vessels
#MMPMID29467494
Roudnicky F
; Yoon SY
; Poghosyan S
; Schwager S
; Poyet C
; Vella G
; Bachmann SB
; Karaman S
; Shin JW
; Otto VI
; Detmar M
Oncogene
2018[May]; 37
(19
): 2573-2585
PMID29467494
show ga
Thrombospondin-2 (TSP2) is an anti-angiogenic matricellular protein that inhibits
tumor growth and angiogenesis. Tumor-associated blood vascular endothelial cells
(BECs) were isolated from human invasive bladder cancers and from matched normal
bladder tissue by immuno-laser capture microdissection. Exon expression profiling
analyses revealed a particularly high expression of a short TSP2 transcript
containing only the last 9 (3') exons of the full-length TSP2 transcript. Using
5' and 3' RACE (rapid amplification of cDNA ends) and Sanger sequencing, we
confirmed the existence of the shorter transcript of TSP2 (sTSP2) and determined
its sequence which completely lacked the anti-angiogenic thrombospondin type 1
repeats domain. The largest open reading frame predicted within the transcript
comprises 209 amino acids and matches almost completely the C-terminal lectin
domain of full-length TSP2. We produced recombinant sTSP2 and found that unlike
the full-length TSP2, sTSP2 did not inhibit vascular endothelial growth
factor-A-induced proliferation of cultured human BECs, but in contrast when
combined with TSP2 blocked the inhibitory effects of TSP2 on BEC proliferation.
In vivo studies with stably transfected A431 squamous cell carcinoma cells
revealed that full-length TSP2, but not sTSP2, inhibited tumor growth and
angiogenesis. This study reveals that the transcriptional program of tumor
stromal cells can change to transcribe a new version of an endogenous
angiogenesis inhibitor that has lost its anti-angiogenic activity.