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Tumor Invasion and Metastasis

Invasio et metastasis tumorum

For medical students2 min readUpdated 2026-10-10

Invasion is the ability of tumor cells to infiltrate surrounding tissues, while metastasis is the process of their spread to distant organs. These processes are key stages in the morphogenesis of malignant neoplasms.

Invasion PhasesThe process involves three stages: transformation, matrix degradation, and cell migration.
Metastatic PathwaysMajor pathways include lymphatic, hematogenous, perineural, and implantation.
Genetic ControlTranscription factors SNAIL and TWIST promote epithelial-mesenchymal transition.
Cancer OsteolysisBreast cancer bone metastases activate osteoclasts via PTHRP and RANK ligand.

Stages of Tumor Invasion

Invasion is the active penetration of a tumor into healthy tissues, progressing through three sequential stages:

  1. Epithelial-Mesenchymal Transition (EMT): Cells lose intercellular junctions and become more motile. Expression of integrins increases, allowing cells to anchor to matrix components.
  2. Matrix Degradation: Tumor cells secrete proteolytic enzymes that literally carve a path through the extracellular matrix.
  3. Migration: Matrix breakdown products (fibronectin, laminin) act as chemoattractants, drawing tumor cells toward the area of destruction.

The Metastatic Cascade

The spread of a tumor to distant organs occurs via a complex chain of events known as the metastatic cascade:

Molecular Mechanisms of Osteolysis

When breast cancer metastasizes to bones, a specific bone destruction mechanism is triggered:

ComponentRole
PTHRPSecreted by the tumor, stimulates osteoblasts
RANK LigandProduced by osteoblasts, activates osteoclasts
OsteoclastsDegrade the bone matrix

As a result of bone destruction, growth factors (IGF, TGF-$eta$) are released, which further promote tumor growth.

Mnemonic

To remember the phases of invasion, use the formula "Transformation — Degradation — Migration" (TDM).

Frequently asked questions

What enzymes do tumor cells secrete to degrade the extracellular matrix?

Tumor cells secrete proteolytic enzymes and their activators to degrade the extracellular matrix and clear the path for invasion.

Enzymes produced by tumor cells include:

  • Collagenases.
  • Elastases.

Active synthesis of collagenases and elastases shifts the dynamic balance, promoting infiltrative growth and tumor penetration into adjacent tissues.

Which adhesion molecules change their expression during epithelial-mesenchymal transition?

During epithelial-mesenchymal transition, the expression of several groups of adhesion molecules changes, ensuring cell mobility. The following changes occur:

  • CD44 family molecules — their concentration decreases, leading to weakened intercellular connections.
  • Integrins — their expression increases, securing cell attachment to extracellular matrix components (laminin, fibronectin, collagens).

Additionally, cytoskeletal remodeling disrupts the interaction of integrins and cadherins with the extracellular matrix, facilitating invasive growth.

Which malignant tumors are most commonly associated with hematogenous metastasis?

The hematogenous pathway of metastasis is cited in sources for the following malignant tumors:

  • Liposarcoma — metastasizes hematogenously to internal organs.
  • Synovial sarcoma — rapidly gives rise to lymphatic and hematogenous metastases.
  • Ewing sarcoma — metastasizes early; hematogenous spread to the lungs and lymph nodes is noted.
  • Peripheral lung cancer — hematogenous metastasis is typical for late stages; metastases are found in the liver, bones, adrenal glands, and brain.
  • Cervical cancer — hematogenous metastases are most frequently found in the lungs, liver, and bones.

Furthermore, hematogenous spread to the heart is noted in systemic tumors: malignant melanoma, lymphoma, leukemia, sarcoma, and carcinoma.

What is implantation metastasis and for which localizations is it characteristic?

Implantation metastasis is the spread of tumor cells along serous membranes or the implantation of tumor cells present in body fluids onto organ surfaces.

It occurs in two ways:

  • Contact — direct touch of a tumor cell with unaffected tissue or organ; examples include gastric cancer cells spreading to the peritoneum or lung cancer cells to the pleura.
  • Implantation via fluids — implantation of blastoma cells from cerebrospinal fluid or exudate within serous cavities.

Characteristic localizations include the abdominal and thoracic cavities, and the meninges. Implantation metastasis can lead to peritoneal carcinomatosis, a variant noted, for example, in cervical cancer.

What is epithelial-mesenchymal transition?

It is a process whereby tumor cells lose epithelial properties, weaken intercellular contacts, and acquire mobility characteristic of mesenchymal cells.

Which genes are responsible for metastasis?

Key candidates are the SNAIL and TWIST genes, which encode transcription factors that trigger the shift of tumor cells toward a metastatic phenotype.

How does the lymphatic pathway differ from the hematogenous pathway?

The lymphatic pathway involves the spread of cells via lymphatic vessels (potentially retrograde), while the hematogenous pathway occurs via blood vessels.

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