Blood tumor barrier
As blood-tumor barrier ( Engl. Blood-tumor barrier ) refers to the physiological barrier between the bloodstream and a solid malignant (malignant) tumor .
description
The blood-tumor barrier, like the blood-brain barrier , is formed by endothelial cells . The blood vessels lined by the endothelial cells for supplying a tumor with nutrients and oxygen are significantly more permeable than the continuous endothelium, which ensures the supply of normal, non-degenerate tissue. Basically, the blood vessels of tumors have much wider open intercellular connection complexes ( tight junctions ), a larger number of openings (fenestrations) and endocytotic vesicles . The basal lamina is interrupted or completely absent. These structural changes increase the throughput of molecules via the blood vessels to the tumor, which in turn causes increased interstitial pressure in the tumor and reduced microvascular pressure. The interstitial pressure in human tumors can be up to 50 mm Hg higher than that in normal tissue.
The changes in the endothelium are caused by the tumor itself. The vascular permeability factor (VEGF) plays an important role . This growth factor is released from the tumor to the surrounding tissue and increases the permeability of the blood vessels.
Effects
The changes in the pressure conditions in the tumor result in a delayed extravasation of molecules and cells, especially in larger tumors. These properties of the blood-tumor barrier influence tumor growth and its metastasis , as well as the diagnosis and therapy of the tumor.
The increased interstitial pressure makes it more difficult, for example, for cytostatics to penetrate the tumor tissue via the blood vessels. The leaks in the blood-tumor barrier also make the transport of active substances to the tumor more difficult.
The increased fenestration of the endothelium at the blood-tumor barrier, on the other hand, is used with the so-called EPR effect for passive drug targeting , i.e. for the targeted transport of active substances using macromolecules or nanoparticles .
further reading
- PR Lockman, RK Mittapalli et al: Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer. In: Clinical Cancer Research . Volume 16, Number 23, December 2010, pp. 5664-5678, ISSN 1078-0432 . doi : 10.1158 / 1078-0432.CCR-10-1564 . PMID 20829328 . PMC 2999649 (free full text).
- M. Manzur, J. Hamzah, R. Ganss: Modulation of the "blood-tumor" barrier improves immunotherapy. In: Cell cycle. Volume 7, Number 16, August 2008, pp. 2452-2455, ISSN 1551-4005 . PMID 18719382 .
- DR Groothuis: The blood-brain and blood-tumor barriers: a review of strategies for increasing drug delivery. In: Neuro-Oncology . Volume 2, Number 1, January 2000, pp. 45-59, ISSN 1522-8517 . PMID 11302254 . PMC 1920694 (free full text). (Review).
- EV Batrakova, HE Gendelman, AV Kabanov: Cell-mediated drug delivery. In: Expert Opinion on Drug Delivery . Volume 8, Number 4, April 2011, pp. 415-433, ISSN 1744-7593 . doi : 10.1517 / 17425247.2011.559457 . PMID 21348773 . PMC 3062753 (free full text). (Review).
Individual evidence
- ↑ H. Sarin, AS Kanevsky et al. a .: Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors. In: Journal of translational medicine. Volume 7, 2009, p. 51, ISSN 1479-5876 . doi : 10.1186 / 1479-5876-7-51 . PMID 19549317 . PMC 2706803 (free full text).
- ↑ R. Kubale, H. Stiegler: Color-coded duplex sonography. Georg Thieme Verlag, 2002, ISBN 3-131-28651-2 , p. 499. Restricted preview in the Google book search
- ^ WG Roberts, GE Palade: Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. In: Journal of cell science. Volume 108 (Pt 6), June 1995, pp. 2369-2379, ISSN 0021-9533 . PMID 7673356 .
- ^ RK Jain: Transport of molecules across tumor vasculature. In: Cancer Metastasis Reviews . Volume 6, Number 4, 1987, pp. 559-593, ISSN 0167-7659 . PMID 3327633 . (Review).
- ↑ RK Jain: Transport of molecules in the tumor interstitium: a review. In: Cancer Research . Volume 47, Number 12, June 1987, pp. 3039-3051, ISSN 0008-5472 . PMID 3555767 . (Review).
- ^ RK Jain: Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. In: Science . Volume 307, Number 5706, January 2005, pp. 58-62, ISSN 1095-9203 . doi : 10.1126 / science.1104819 . PMID 15637262 . (Review).
- ↑ S. Folli, A. Pèlegrin et al. a .: Tumor-necrosis factor can enhance radio-antibody uptake in human colon carcinoma xenografts by increasing vascular permeability. In: International Journal of Cancer . Volume 53, Number 5, March 1993, pp. 829-836, ISSN 0020-7136 . PMID 8449608 .
- ↑ B. Jacket: The liposomal targeting of aminopeptidase N on angiogenetically active endothelial cells as a possible new therapeutic approach. Dissertation, Martin Luther University Halle-Wittenberg, 2008, p. 9.
- ^ H. Maeda et al: Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. In: J Control Release . Volume 65, 2000, pp. 271-284. PMID 10699287 (Review)