How Do Cancer Cells Enter the Bloodstream?

1. Detachment from the Tumor

Cancer cells first need to break away from the original tumor mass.
This often involves biological changes that make them more mobile and less attached to surrounding tissue.

2. Invasion into Nearby Tissue

After detaching, cancer cells invade surrounding tissue and move toward nearby blood vessels.

3. Entry into Blood Vessels (Intravasation)

Cancer cells then enter the bloodstream through a process called intravasation.
This can occur in two main ways:

• Active entry: Cancer cells actively penetrate blood vessel walls
• Passive entry: Blood vessels become leaky or damaged, allowing cells to slip in

Recent research also suggests that clusters of tumor cells may interact with and disrupt vessel walls, making entry easier.

What Happens Once Cancer Cells Are in the Blood?

4. Survival in Circulation

The bloodstream is a harsh environment. Many cancer cells do not survive due to:

• Immune system attacks
• Physical stress from blood flow

In fact, most circulating tumor cells are eliminated, and only a small fraction survive.

Some cells develop strategies to survive, such as traveling in clusters, which may increase their chances of survival and spread.

5. Exit into New Tissues (Extravasation)

Surviving cancer cells may attach to blood vessel walls and exit into distant tissues.
This step is known as extravasation.

6. Formation of New Tumors (Metastasis)

If these cells successfully adapt to the new environment, they may begin to grow and form secondary tumors.

This entire journey—from tumor to bloodstream to new site—is often called the metastatic cascade.

Why Are Circulating Tumor Cells Important?

CTCs are considered a key part of cancer progression because they:

• May contribute to the spread of cancer to other organs
• May provide insights into how a cancer behaves
• May help researchers study disease progression and response

However, it is important to note that not all circulating tumor cells lead to metastasis. Many are destroyed before they can establish new tumors.

Key Takeaways

• Cancer cells can leave the primary tumor and enter the bloodstream as circulating tumor cells (CTCs)
• This process involves multiple steps: detachment, invasion, intravasation, survival, and colonization
• Most circulating cells do not survive—but a small number may contribute to metastasis
• Understanding this process may help support more personalized approaches to cancer care

References

• Lin, D., et al. (2021). Circulating tumor cells: biology and clinical significance. Signal Transduction and Targeted Therapy, 6, 404.
• Chiang, S. P. H., et al. (2016). Tumor cell intravasation. Cancer Metastasis Reviews.
• Micalizzi, D. S., et al. (2017). A conduit to metastasis: circulating tumor cell biology. Genes & Development.
• Deng, Z., et al. (2022). Circulating tumor cells in cancer diagnosis and prognosis. Biosensors and Bioelectronics.
• Chen, Q., et al. (2022). Circulating tumor cell clusters and metastasis. Frontiers in Oncology.
• Zhou, J. S., et al. (2023). Circulating tumor cells and metastasis mechanisms. Molecular and Clinical Oncology.
• Yang, C., et al. (2025). Clinical applications of circulating tumor cells in metastasis. Frontiers in Oncology.
• Matsunaga, Y., et al. (2025). Tumor clusters entering bloodstream mechanisms. News-Medical.