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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
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Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
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Related Experiment Video

Updated: Apr 19, 2026

Preparation of Exosomes for siRNA Delivery to Cancer Cells
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Hypoxic exosomes promote angiogenesis.

Guo-Chang Fan1

  • 1UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE.

Blood
|December 16, 2014
PubMed
Summary

Exosomal miR-135b is key in multiple myeloma (MM) cell communication with endothelial cells during chronic hypoxia. This finding reveals a novel mechanism in MM progression and potential therapeutic targets.

Area of Science:

  • Hematology
  • Molecular Biology
  • Cancer Research

Background:

  • Multiple myeloma (MM) is a hematologic malignancy.
  • Chronic hypoxia is a hallmark of the tumor microenvironment.
  • Intercellular communication is crucial for MM progression.

Purpose of the Study:

  • To investigate the role of exosomal microRNAs in MM cell-to-endothelial cell communication.
  • To identify specific microRNAs involved in MM pathogenesis under hypoxic conditions.

Main Methods:

  • Isolation and characterization of exosomes from MM cells.
  • Analysis of microRNA content within exosomes.
  • Co-culture experiments with MM cells and endothelial cells under hypoxia.
  • Functional assays to assess the impact of exosomal miR-135b.

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Main Results:

  • Exosomes derived from MM cells contain significant levels of miR-135b.
  • Exosomal miR-135b mediates communication between MM cells and endothelial cells.
  • This communication promotes MM cell survival and proliferation under chronic hypoxia.

Conclusions:

  • Exosomal miR-135b is a critical mediator of MM cell-endothelial cell interactions.
  • Targeting exosomal miR-135b may offer a novel therapeutic strategy for multiple myeloma.