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Metastasis02:30

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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.
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Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
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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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Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
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Updated: Mar 29, 2026

Intra-iliac Artery Injection for Efficient and Selective Modeling of Microscopic Bone Metastasis
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The Lymphatic-Bone Axis in Cancer Metastasis.

Ahlim Lee1,2,3, James Rhee4, Rajeev Malhotra2,3

  • 1Department of Urology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

Cancers
|March 28, 2026
PubMed
Summary
This summary is machine-generated.

Lymph nodes act as

Keywords:
bone metastasishigh endothelial venuleslymph node metastasislymphatic systemlymphatic–bone axisosteomimicry

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Quantification of Tumor Cell Adhesion in Lymph Node Cryosections
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Area of Science:

  • Oncology
  • Cancer Metastasis
  • Lymphatic Biology

Background:

  • Bone metastasis is a major cause of cancer mortality.
  • Current models of skeletal dissemination via hematogenous spread do not fully explain clinical observations.
  • Lymph node metastasis is a strong predictor of bone involvement, suggesting a more active role for lymph nodes.

Purpose of the Study:

  • To introduce the Lymphatic-Bone Axis framework.
  • To synthesize evidence on how lymph nodes prime tumor cells for bone metastasis.
  • To propose future research directions and discuss translational implications.

Main Methods:

  • Review of existing literature and emerging evidence.
  • Synthesis of data on tumor cell priming within the lymph node microenvironment.
  • Discussion of preclinical data on intranodal intravasation.

Main Results:

  • Lymph nodes act as 'evolutionary gateways' that sculpt bone-tropic metastatic clones.
  • The lymph node microenvironment primes tumor cells via CCR7-CXCR4 switching, osteomimicry, and metabolic reprogramming.
  • High endothelial venules (HEVs) provide a direct route for tumor cell entry into circulation.

Conclusions:

  • The Lymphatic-Bone Axis framework integrates lymphatic biology into bone metastasis.
  • Understanding lymphatic priming is crucial for developing effective therapies.
  • Multimodal approaches targeting both lymphatic transit and the bone microenvironment are needed.