Langenkamp E, Kamps JA, Mrug M, Verpoorte E, Niyaz Y, Horvatovich P, Bischoff R, Struijker-Boudier H, Molema G (2013). Innovations in studying in vivo cell behaviour and pharmacology in complex tissues - microvascular endothelial cells in the spotlight. Cell Tissue Res, 354(3):647-69.
The review describes how the complexity of in vivo tissues urges us to study cell biology and drug effects in these environments and how the combination of laser microdissection and novel advancements in read out technologies such as proteomics, kinomics and transcriptomics will contribute to a more effective drug development process.
Dieterich LC, Mellberg S, Langenkamp E, Zhang L, Zieba A, Salomaki H, Teichert M, Huang H, Edqvist PH, Kraus T, Augustin HG, Olofsson T, Larsson E, Soderberg O, Molema G, Ponten F, Georgii-Hemming P, Alafuzoff I, and Dimberg A (2012), Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGF-beta2 in vascular abnormalization. J Pathol, 228 (3):378-390.
Lasermicrodissection of FITC-UEA-1 labeled human glioblastoma vessels and normal brain vessels provided samples for Affymetrix microarray analyses, which revealed that 95 genes were differentially expressed between the glioblastoma and normal vasculature.
Langenkamp E, Zwiers PJ, Moorlag HE, Leenders WP, St Croix B, and Molema G (2012). Vascular endothelial growth factor receptor 2 inhibition in-vivo affects tumor vasculature in a tumor type-dependent way and downregulates vascular endothelial growth factor receptor 2 protein without a prominent role for miR-296. Anticancer Drugs ; 23: 161-172.
Vandetanib (ZD6474) treatment of mice bearing s.c. LLC or B16.F10 melanoma resulted in a more than 80% reduction in tumor outgrowth. The molecular effects (gene and micro-RNA expression) in the tumor vasculatures associated with these anti-tumor effects were unmasked user lasermicrodissection of the vessels prior to qRT-PCR analysis.
Langenkamp E, vom Hagen FM, Zwiers PJ, Moorlag HE, Schouten JP, Hammes HP, Gouw AS, and Molema G (2011), Tumor Vascular Morphology Undergoes Dramatic Changes during Outgrowth of B16 Melanoma While Proangiogenic Gene Expression Remains Unchanged. ISRN Oncology ePub:article ID 409308.
Sikkema AH, de Bont ES, Molema G, Dimberg A, Zwiers PJ, Diks SH, Hoving EW, Kamps WA, Peppelenbosch MP, and den Dunnen WF (2011). VEGFR-2 signalling activity in paediatric pilocytic astrocytoma is restricted to tumour endothelial cells. Neuropathol Appl Neurobiol; 37(5): 538-548.
Vascular and tissue behavior in disease:
Katta K, Boersema M, Adepu S, Rienstra H, Celie JW, Mencke R, Molema G, van Goor H, Berden JH, Navis G, Hillebrands JL, van den Born J (2013). Renal heparan sulphate proteoglycans modulate fibroblast growth factor 2 signaling in experimental chronic transplant dysfunction. Am J Pathol, 183(5):1571-84.
Dickinson MG, Bartelds B, Molema G, Borgdorff MA, Boersma B, Takens J, Weij M, Wichers P, Sietsma H, and Berger RM (2011). Egr-1 expression during neointimal development in flow-associated pulmonary hypertension. Am J Pathol; 179: 2199-2209.
van Meurs M, Fisheri NK, Wulfert FM, Asgeirsdottir SA, de Graaf IA, Satchell SC, Mathieson PW, Jongman RM, Kumpers P, Zijlstra JG, Heeringa P, and Molema G (2009). Shock induced stress induces loss of microvascular endothelial Tie2 in the kidney which is not associated with reduced glomerular barrier function. Am.J Physiol Renal Physiol 297 (2): F272-281.
Molecular control of microvascular behavior in vivo:
Asgeirsdottir SA, van SC, Kurniati NF, Zwiers PJ, Heeringa P, van MM, Satchell SC, Saleem MA, Mathieson PW, Banas B, Kamps JA, Rabelink TJ, van Zonneveld AJ, and Molema G (2012), MicroRNA-126 contributes to renal microvascular heterogeneity of VCAM-1 protein expression in acute inflammation. Am J Physiol Renal Physiol; 302(12):F1630-9.
Yuan L, Sacharidou A, Stratman AN, Le Bras A, Zwiers PJ, Spokes K, Bhasin M, Shih SC, Nagy JA, Molema G, Aird WC, Davis GE, and Oettgen P (2011). RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG. Blood; 118(4):1145-1153.
Asgeirsdottir SA, Kamps JAAM, Bakker HI, Zwiers PJ, Heeringa P, van der Weide K, Van Goor H, Petersen AH, Morselt HW, Moorlag HE, Steenbergen E, Kallenberg CGM, and Molema G (2007), Site-specific inhibition of glomerulonephritis progression by targeted delivery of dexamethasone to glomerular endothelium. Mol Pharmacol 72(1): 121-131.