Abnormalities in Pericytes on Blood Vessels and Endothelial Sprouts in Tumors
Shunichi Morikawa,Peter Baluk,Toshiyuki Kaidoh,Amy Haskell,Rakesh K. Jain,Donald M. McDonald +5 more
TLDR
It is concluded that pericytes are present on most tumor vessels but have multiple abnormalities, including altered expression of marker proteins, which raises the possibility of an involvement in sprout growth or retraction in tumors.Abstract:
Endothelial cells of tumor vessels have well-documented alterations, but it is less clear whether pericytes on these vessels are abnormal or even absent. Here we report that α-smooth muscle actin (α-SMA) and desmin-immunoreactive pericytes were present on >97% of blood vessels viewed by confocal microscopy in 100-μm-thick sections of three different spontaneous or implanted tumors in mice. However, the cells had multiple abnormalities. Unlike pericytes on capillaries in normal pancreatic islets, which had desmin but not α-SMA immunoreactivity, pericytes on capillary-size vessels in insulinomas in RIP-Tag2 transgenic mice expressed both desmin and α-SMA. Furthermore, pericytes in RIP-Tag2 tumors, as well as those in MCa-IV breast carcinomas and Lewis lung carcinomas, had an abnormally loose association with endothelial cells and extended cytoplasmic processes deep into the tumor tissue. α-SMA-positive pericytes also covered 73% of endothelial sprouts in RIP-Tag2 tumors and 92% of sprouts in the other tumors. Indeed, pericyte sleeves were significantly longer than the CD31-immunoreactive endothelial cell sprouts themselves in all three types of tumors. All three tumors also contained α-SMA-positive myofibroblasts that resembled pericytes but were not associated with blood vessels. We conclude that pericytes are present on most tumor vessels but have multiple abnormalities, including altered expression of marker proteins. In contrast to some previous studies, the almost ubiquitous presence of pericytes on tumor vessels found in the present study may be attributed to our use of both desmin and α-SMA as markers and 100-μm-thick tissue sections. The association of pericytes with endothelial sprouts raises the possibility of an involvement in sprout growth or retraction in tumors.read more
Citations
More filters
Journal ArticleDOI
Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment
Douglas Hanahan,Lisa M. Coussens +1 more
TL;DR: Most of the hallmarks of cancer are enabled and sustained to varying degrees through contributions from repertoires of stromal cell types and distinctive subcell types, which presents interesting new targets for anticancer therapy.
Journal ArticleDOI
Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease
TL;DR: The focus of this review is to provide an overview of the current state of knowledge of molecular mechanisms/processes that control differentiation of vascular smooth muscle cells (SMC) during normal development and maturation of the vasculature, as well as how these mechanisms/ processeses are altered in vascular injury or disease.
Journal ArticleDOI
Tumorigenesis and the angiogenic switch
TL;DR: A more detailed understanding of the complex parameters that govern the interactions between the tumour and vascular compartments will help to improve anti-angiogenic strategies — not only for cancer treatment, but also for preventing recurrence.
Journal ArticleDOI
Molecular regulation of vessel maturation.
TL;DR: The maturation of nascent vasculature, formed by vasculogenesis or angiogenesis, requires recruitment of mural cells, generation of an extracellular matrix and specialization of the vessel wall for structural support and regulation of vessel function.
Journal ArticleDOI
Pericytes: developmental, physiological, and pathological perspectives, problems, and promises.
TL;DR: The history of investigations into pericytes, the mural cells of blood microvessels, are reviewed, emerging concepts are indicated, and problems and promise are pointed out.
References
More filters
Journal ArticleDOI
Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a lewis lung carcinoma
Michael S. O'Reilly,Michael S. O'Reilly,Lars Holmgren,Lars Holmgren,Yuen Shing,Yuen Shing,Catherine Chen,Catherine Chen,Rosalind A. Rosenthal,Rosalind A. Rosenthal,Marsha A. Moses,Marsha A. Moses,William S. Lane,Yihai Cao,E. Helene Sage,Judah Folkman +15 more
TL;DR: It is shown that the inhibition of metastases by a primary mouse tumor is mediated, at least in part, by angiostatin, and a corresponding fragment of human plasminogen has similar activity.
Journal ArticleDOI
Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment
Susan K. Hobbs,Wayne L. Monsky,Fan Yuan,W. G. Roberts,Linda G. Griffith,Vladimir P. Torchilin,Rakesh K. Jain +6 more
TL;DR: Delivery may be less efficient in cranial tumors than in subcutaneous tumors, delivery may be reduced during tumor regression induced by hormonal ablation, and permeability to a molecule is independent of pore cutoff size as long as the diameter of the molecule is much less than the pore diameter.
Journal ArticleDOI
Cancer Treatment by Targeted Drug Delivery to Tumor Vasculature in a Mouse Model
TL;DR: In vivo selection of phage display libraries was used to isolate peptides that home specifically to tumor blood vessels that enhanced the efficacy of the anticancer drug doxorubicin and reduced its toxicity.
Journal ArticleDOI
Pericyte Loss and Microaneurysm Formation in PDGF-B-Deficient Mice
TL;DR: Comparisons made between PDGF null mouse phenotypes suggest a general role for PDGFs in the development of myofibroblasts, and endothelial cells of the sprouting capillaries in the mutant mice appeared to be unable to attract PDGF-Rbeta-positive pericyte progenitor cells.
Journal ArticleDOI
Genes expressed in human tumor endothelium
Brad St. Croix,Carlo Rago,Carlo Rago,Victor E. Velculescu,Giovanni Traverso,Katharine E. Romans,Elizabeth A. Montgomery,Anita Lal,Gregory J. Riggins,Christoph Lengauer,Bert Vogelstein,Bert Vogelstein,Kenneth W. Kinzler +12 more
TL;DR: It is demonstrated that tumor and normal endothelium are distinct at the molecular level, a finding that may have significant implications for the development of anti-angiogenic therapies.