Extracellular matrix constituents interfere with Newcastle disease virus spread in solid tissue and diminish its

Barak Yaacov1, Itay Lazar2, Shay Tayeb1

  • 1Department of Biochemistry, the Chanock Center for Virology, IMRIC, Hadassah Medical Center-Hebrew University, Jerusalem 91120, Israel.

Insights

Newcastle disease virus (NDV) shows oncolytic potential against advanced melanoma. However, extracellular matrix molecules in solid tumors like melanoma and lung carcinoma limit NDV

Area of Science:

  • Oncology
  • Virology
  • Biotechnology

Background:

  • Advanced melanoma and lung carcinoma exhibit chemotherapy resistance.
  • Newcastle disease virus (NDV) demonstrates oncolytic activity against cancer cells.
  • Understanding NDV's efficacy in solid tumors requires investigating its infectivity and spread.

Purpose of the Study:

  • To evaluate the capacity of Newcastle disease virus (NDV) to infect and spread within solid human melanoma and lung carcinoma tissues.
  • To assess the oncolytic activity of different NDV strains in vivo and ex vivo models.
  • To identify potential barriers to viral spread within solid tumors.

Main Methods:

  • Development of a SCID-beige mouse model with human melanoma xenografts.
  • In vivo and ex vivo analysis of NDV strains (NDV-MTH and NDV-HUJ) in melanoma and lung carcinoma tissues.
  • Investigation of extracellular matrix (ECM) components' role in limiting viral dissemination.

Main Results:

  • Both replication-competent and attenuated NDV strains showed similar oncolytic activity in melanoma-bearing mice.
  • Ex vivo analysis revealed limited spread of NDV within melanoma and lung carcinoma tissues.
  • Extracellular matrix molecules, including heparin sulfate and collagen, were identified as barriers restricting viral spread.

Conclusions:

  • The extracellular matrix (ECM) in solid tumors acts as a significant barrier to Newcastle disease virus (NDV) spread.
  • Overcoming ECM-mediated restriction is crucial for enhancing NDV's oncolytic efficacy in solid tumors.
  • Further research should focus on strategies to mitigate ECM barriers for effective viral oncolysis.

Related Concept Videos

Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
The Extracellular Matrix01:29

The Extracellular Matrix

Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
Cytotoxic Edema: Pathophysiology01:21

Cytotoxic Edema: Pathophysiology

Cytotoxic edema is a form of cerebral edema characterized by intracellular swelling of neurons, astrocytes, and other glial cells. It develops when the mechanisms responsible for maintaining ionic gradients across the cell membrane become impaired. Under normal physiological conditions, the sodium–potassium ATPase actively transports sodium ions out of the cell and potassium ions into the cell, preserving osmotic balance and enabling electrical signaling. This pump requires a continuous supply...