Vascular mimicry in glioblastoma following anti-angiogenic and anti-20-HETE therapies

Kartik Angara, Mohammad H. Rashid, Adarsh Shankar, Roxan Ara, Asm Iskander, Thaiz Ferraz Borin, Meenu Jain, Bhagelu Ram Achyut, Ali Syed Arbab

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Glioblastoma (GBM) is one hypervascular and hypoxic tumor known among solid tumors. Antiangiogenic therapeutics (AATs) have been tested as an adjuvant to normalize blood vessels and control abnormal vasculature. Evidence of relapse exemplified in the progressive tumor growth following AAT reflects development of resistance to AATs. Here, we identified that GBM following AAT (Vatalanib) acquired an alternate mechanism to support tumor growth, called vascular mimicry (VM). We observed that Vatalanib induced VM vessels are positive for periodic acid-Schiff (PAS) matrix but devoid of any endothelium on the inner side and lined by tumor cells on the outer-side. The PAS+ matrix is positive for basal laminae (laminin) indicating vascular structures. Vatalanib treated GBM displayed various stages of VM such as initiation (mosaic), sustenance, and full-blown VM. Mature VM structures contain red blood cells (RBC) and bear semblance to the functional blood vessel-like structures, which provide all growth factors to favor tumor growth. Vatalanib treatment significantly increased VM especially in the core of the tumor, where HIF-1α was highly expressed in tumor cells. VM vessels correlate with hypoxia and are characterized by co-localized MHC-1+ tumor and HIF-1α expression. Interestingly, 20-HETE synthesis inhibitor HET0016 significantly decreased GBM tumors through decreasing VM structures both at the core and at periphery of the tumors. In summary, AAT induced resistance characterized by VM is an alternative mechanism adopted by tumors to make functional vessels by transdifferentiation of tumor cells into endothelial-like cells to supply nutrients in the event of hypoxia. AAT induced VM is a potential therapeutic target of the novel formulation of HET0016. Our present study suggests that HET0016 has a potential to target therapeutic resistance and can be combined with other antitumor agents in preclinical and clinical trials.

Original languageEnglish (US)
Pages (from-to)917-928
Number of pages12
JournalHistology and Histopathology
Volume32
Issue number9
DOIs
StatePublished - Jan 1 2017

Fingerprint

Glioblastoma
Blood Vessels
Neoplasms
Therapeutics
Periodic Acid
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Growth
Cell Transdifferentiation
Laminin
Basement Membrane
Vascular Resistance
Antineoplastic Agents
Endothelium
Intercellular Signaling Peptides and Proteins
Endothelial Cells
Erythrocytes
Clinical Trials

Keywords

  • 20-HETE
  • Angiogenesis
  • Anti-antiogenic therapy HET0016
  • Glioblastoma
  • Vascular mimicry
  • Vasculogenesis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Vascular mimicry in glioblastoma following anti-angiogenic and anti-20-HETE therapies. / Angara, Kartik; Rashid, Mohammad H.; Shankar, Adarsh; Ara, Roxan; Iskander, Asm; Borin, Thaiz Ferraz; Jain, Meenu; Achyut, Bhagelu Ram; Arbab, Ali Syed.

In: Histology and Histopathology, Vol. 32, No. 9, 01.01.2017, p. 917-928.

Research output: Contribution to journalArticle

Angara, K, Rashid, MH, Shankar, A, Ara, R, Iskander, A, Borin, TF, Jain, M, Achyut, BR & Arbab, AS 2017, 'Vascular mimicry in glioblastoma following anti-angiogenic and anti-20-HETE therapies', Histology and Histopathology, vol. 32, no. 9, pp. 917-928. https://doi.org/10.14670/HH-11-856
Angara, Kartik ; Rashid, Mohammad H. ; Shankar, Adarsh ; Ara, Roxan ; Iskander, Asm ; Borin, Thaiz Ferraz ; Jain, Meenu ; Achyut, Bhagelu Ram ; Arbab, Ali Syed. / Vascular mimicry in glioblastoma following anti-angiogenic and anti-20-HETE therapies. In: Histology and Histopathology. 2017 ; Vol. 32, No. 9. pp. 917-928.
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AU - Iskander, Asm

AU - Borin, Thaiz Ferraz

AU - Jain, Meenu

AU - Achyut, Bhagelu Ram

AU - Arbab, Ali Syed

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