Tumor Metastasis

Routes of metastasis spread

Malignant neoplasms can spread through the body via several routes, and they are often involved simultaneously or sequentially.

• Contact route: a tumor cell comes into direct contact with unaffected tissue. A characteristic example is the spread of gastric cancer cells to the peritoneum or lung cancer to the pleura.
• Implantation route: blastoma cells are transported via body fluids (cerebrospinal fluid, exudate). This usually occurs in serous cavities (thoracic, abdominal) or on the meninges of the brain and spinal cord.

Stages of vascular metastasis

The process of cell transport via blood and lymphatic vessels includes four strict stages:

1. Detachment and intravasation. A malignant cell detaches from the primary node, invades the microvessel wall, and enters its lumen.
2. Embolism. The cell circulates in the blood or lymph flow, after which it attaches (adhesion occurs) to the vascular endothelium at a new site.
3. Extravasation. The tumor cell destroys the vessel wall from the inside and enters the surrounding healthy tissue.
4. Metastasis formation. The blastoma begins to divide actively, forming a secondary node identical to the parent tumor.

Organ selectivity (tropism)

Metastases do not spread randomly — they exhibit "homing," meaning a tendency to affect specific organs. For example, lung cancer frequently metastasizes to the bones, liver, and brain, while gastric cancer metastasizes to the pelvic floor tissues and ovaries (so-called Krukenberg tumor).

This selectivity depends on several factors:

• Metabolic conditions: the specific metabolism in the target organ must be favorable for a particular tumor.
• Anatomical pathways: features of local blood and lymph circulation.
• Impaired local immunity: low efficacy of anti-blastoma resistance mechanisms in the tissue.
• Positive chemotaxis: chemical attraction of malignant cells.

Epithelial-mesenchymal transition (EMT)

EMT plays an important role in metastatic potential. During this process, cells activate embryonic genes, enabling them to migrate actively.

For example, in melanoma, a switch in cell-cell adhesion protein expression occurs: E-cadherin (responsible for connection with epithelium and keratinocytes) is replaced by N-cadherin (provides contact with mesenchymal cells). As a result, melanocytes lose contact with their microenvironment, begin to interact with epidermal growth factor, and purposefully move toward vessel walls.

Tumor progression and recurrence

Tumor progression is an irreversible, genetically fixed change in cell properties that is inherited (the phenomenon was first described by L. Foulds in 1969). Due to high genotype variability, the tumor becomes heterogeneous. Different cell clones are formed, allowing the blastoma to adapt to hypoxia, nutrient deficiency, or drug action (treatment escape phenomenon). The result of progression is an increase in the degree of atypia and malignancy.

Recurrence is a typical form of growth in which a tumor redevelops in the same site after removal. The causes lie either in surviving viable cells (due to incomplete excision or early invasion) or in the genetic transformation of neighboring normal cells. According to the hypothesis, DNA segments with oncogenes from the destroyed blastoma can integrate into the genome of healthy cells.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of tumor cell invasion into the vascular wall
• The role of chemotaxis in establishing organ tropism
• The phenomenon of blastoma clonal selection (according to L. Foulds)
• The hypothesis of genetic transformation of normal cells during recurrence
• The effect of hypoxia on tumor progression

Other topics in "Chapter 17. NEOPLASMS"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.