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Related Concept Videos

Hypoxia01:23

Hypoxia

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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%.
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
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Osteoclasts in Bone Remodeling01:31

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Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
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Bone Disorders01:29

Bone Disorders

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Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
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Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
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What is the Skeletal System?01:02

What is the Skeletal System?

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Overview
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Bone Remodeling01:40

Bone Remodeling

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Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
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Related Experiment Video

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In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis
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In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis

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Hypoxia in bone metastasis and osteolysis.

Vera M Todd1, Rachelle W Johnson2

  • 1Graduate Program in Cancer Biology, Vanderbilt University, Nashville, TN, USA; Vanderbilt Center for Bone Biology, Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.

Cancer Letters
|June 21, 2020
PubMed
Summary

Hypoxia, or low oxygen, in tumors fuels cancer spread and bone metastasis. Hypoxia-inducible factor (HIF) signaling drives tumor invasion and creates a pre-metastatic niche in bone, worsening patient outcomes.

Keywords:
CancerDormancyHIFOxygenVasculature

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Area of Science:

  • Oncology
  • Cell Biology
  • Pathophysiology

Background:

  • Hypoxia is prevalent in solid tumors and linked to poor prognosis.
  • Hypoxia-inducible factor (HIF) signaling is activated by low oxygen conditions.
  • Tumor-associated hypoxia promotes cancer progression and metastasis.

Purpose of the Study:

  • To investigate the role of hypoxia and HIF signaling in cancer metastasis, particularly to bone.
  • To elucidate the mechanisms by which hypoxia influences the primary tumor and the bone microenvironment.
  • To understand how hypoxia contributes to the formation of a pre-metastatic niche and osteolysis.

Main Methods:

  • Review of experimental evidence on hypoxia and cancer metastasis.
  • Analysis of clinical data linking HIF expression to patient outcomes.
  • Investigation of molecular pathways involved in hypoxia-driven metastasis.

Main Results:

  • Hypoxia drives epithelial-to-mesenchymal transition, invasion, and metastasis.
  • HIF signaling in primary tumors promotes bone dissemination and osteolysis via factors like LOX.
  • The bone microenvironment's hypoxia activates HIF, enhancing tumor cell homing and osteoclastogenesis.
  • Hypoxia contributes to a cycle of bone destruction and tumor growth, and regulates tumor dormancy.

Conclusions:

  • Hypoxia is a critical driver of cancer metastasis to bone.
  • HIF signaling acts on both tumor cells and the bone microenvironment to facilitate metastasis.
  • Targeting hypoxia and HIF pathways may offer therapeutic strategies against metastatic cancer.