Metastasis is a complex process that involves the spread of a tumor or cancer to distant parts of the body from its original site. However, this is a difficult process. To successfully colonize a distant area in the body a cancer cell must complete a series of steps before it becomes a clinically detectable lesion.
Metastasis
Steps of metastasis
The steps of metastasis include:
- separation from the primary tumor
- invasion through tissues around the initial lesion and penetration of their basement membranes
- entry into the blood vessels and survival within blood - spread via blood vessels is called hematogenous spread
- entry into lymphatics or peritoneal cavity - spread via lymph channels is called lymphatic spread
- reaching the distant organ like lungs, liver, brain bone etc.
- formation of a new lesion along with new blood vessels feeding the tumor - formation of new blood vessels is termed angiogenesis
All this while, the cancer cells have to avoid being killed by the body’s natural immune system.
Routes of metastasis
There are four possible routes of spread of cancer. These include:
- spread via lymphatic channels – this is favoured by most carcinomas
- spread via blood vessels – this is favoured by sarcomas and some carcinomas that originate in the kidneys - because of their thinner walls veins are more frequently invaded than arteries and the spread is via veins
- spread via body cavities – the cancer cells seed onto peritoneal (covering the gut and stomach and other abdominal organs), pleural (covering the lungs), pericardial (covering the heart) or subarchnoid spaces (covering the brain) and membranes
- transplantation of the cancer – this occurs by carriage of fragments of tumor cells via needles or surgical instruments to other parts of the body during surgery and diagnostic procedures
Why is metastasis dangerous?
Metastasis is of great importance since most of the cancer deaths are caused by spread of the primary cancer to distant sites. In most cases, cancer patients with localized tumors have a better chance at survival than those with metastatic tumors.
New evidence shows that 60% to 70% of patients have initiated the metastatic process by the time of diagnosis. In addition, even patients that have no evidence of tumor spread at diagnosis are at risk for metastatic disease and need to be treated accordingly.
Metastasis “seed and soil theory” and organs susceptible
Metastasis is one of three hallmarks of malignancy or cancer as opposed to a benign tumor. Most tumors and other neoplasms can metastasize. The degree of ability to spread, however, varies between different types of tumors. For example, basal cell carcinoma rarely spreads.
Some organs are more prone than others to metastasis of primary tumors. This was first discussed as the "seed and soil" theory by Stephen Paget over a century ago in 1889. For example, bones are the favoured site for prostate cancer, colon cancer spreads to liver, stomach cancer can metastasize to the ovaries and is then called Krukenberg tumor.
The theory states that cancer cells find survival outside their primary suites difficult. To spread they need to find a location with similar characteristics. For example, breast cancer cells need calcium ions from breast milk to proliferate. Thus they may prefer the bones as a site of spread as bones are rich in calcium. Malignant melanoma favors melanocytes and nerves and thus may spread to the brain since the neural tissue and melanocytes arise from the same cell line in the embryo.
Challenges to the “seed and soil” theory
This “seed and soil” theory was challenged by James Ewing in 1928 who suggested that metastasis occurs purely by anatomic and mechanical routes. He suggested the spread via lymphatic channels and blood vessels. He noted that cancer cells affected the regional lymph nodes near the primary tumor. This is called nodal involvement, positive nodes, or regional disease.
Primary tumors need biopsies of at least two lymph nodes near a tumor site when doing surgery to examine or remove a tumor. Localized spread to regional lymph nodes near the primary tumor is not normally counted as metastasis, although this is a sign of poor outcome.
Further Reading
Liver cells effectively serve as immune checkpoint regulating anti-cancer immunity