Related Experiment Video

Updated: Jul 14, 2026

Models of Bone Metastasis
08:49

Models of Bone Metastasis

Published on: September 4, 2012

Platelet and osteoclast beta3 integrins are critical for bone metastasis

Suzanne J Bakewell1, Patrick Nestor, Srinivasa Prasad

  • 1Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR and Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 13, 2003
PubMed

Insights

Platelet integrin alphaIIbbeta3 is critical for tumor cells entering bone and causing osteolytic metastasis. Inhibiting this integrin may prevent solid tumor spread and bone destruction.

Area of Science:

  • Oncology
  • Integrin Biology
  • Bone Metastasis Research

Background:

  • Tumor metastasis to bone is a significant cause of morbidity.
  • Integrins play roles in cell adhesion and migration, crucial for metastasis.
  • The specific role of beta3 integrin in bone metastasis and destruction is not fully understood.

Purpose of the Study:

  • To investigate the role of beta3 integrin in tumor cell metastasis to bone.
  • To determine the contribution of beta3 integrin in osteolytic bone destruction.
  • To elucidate the specific cellular sources (osteoclasts vs. platelets) of beta3 integrin involved in bone metastasis.

Main Methods:

  • Utilized beta3 integrin knockout (beta3-/-) mice and wild-type (beta3+/+) littermates.
  • Administered B16 melanoma cells via cardiac ventricle injection and intratibial inoculation.
  • Employed bone marrow transplantation studies and osteoclast-defective src-/- mice.
  • Tested the effect of a specific alphaIIbbeta3 platelet aggregation inhibitor.

Main Results:

  • Beta3 integrin deletion significantly reduced osteolytic bone metastasis following intravenous tumor cell injection.
  • Intratibial tumor inoculation in beta3-/- mice showed tumor growth without bone resorption.
  • Src-null mice were protected from bone destruction but not metastasis, indicating osteoclasts are key to destruction, not entry.
  • Platelet alphaIIbbeta3 inhibition effectively prevented tumor metastasis to bone.

Conclusions:

  • Platelet alphaIIbbeta3 integrin is essential for tumor cell entry into bone, driving metastasis.
  • Osteoclast beta3 integrin is critical for tumor-induced bone resorption but not for initial tumor cell homing to bone.
  • Targeting platelet alphaIIbbeta3 represents a potential therapeutic strategy to prevent solid tumor metastasis to bone.

More Related Videos

Intra-iliac Artery Injection for Efficient and Selective Modeling of Microscopic Bone Metastasis07:00

Intra-iliac Artery Injection for Efficient and Selective Modeling of Microscopic Bone Metastasis

Published on: September 26, 2016

An In Vitro Assay to Study Platelet Migration Using RGD-Functionalized Avidin-Biotin Tethers05:43

An In Vitro Assay to Study Platelet Migration Using RGD-Functionalized Avidin-Biotin Tethers

Published on: November 8, 2024

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...
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
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...
Selectins01:25

Selectins

Cell adhesion is  an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain, which...
Formation of the Platelet Plug01:22

Formation of the Platelet Plug

The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...