Liquid and Solid Tumours

Uncontrolled cell growth and subsequent abnormal accumulation of cells is a property all cancers share. Depending on how exactly this manifests, cancers can be divided into liquid and solid tumours.

Given that solid tumours make up roughly 90% of tumour cases in adults (1), this is also the type most people imagine when they hear the word 'tumour'. They are characterised by localised accumulation of cancer cells in a cohesive (or solid) mass of cancer cells. Even in the case of a metastatic cancer, where it has spread to multiple sites within the body, each of the separate cancer lesions will contain a cohesive mass of cells (2).

In contrast, liquid tumours do not accumulate locally in tissues, but rather accumulate in circulation throughout the body using the blood and lymphatic system. Because of this, they don't form cohesive masses (3).

We know that cells in general, as well as their behaviour, are extremely dependent on their surroundings. All the healthy cells in a human body share the same genome. Despite this, they are able to produce completely different proteins, display different behaviours and fulfil different functions. This happens because the context in which cells find themselves heavily impacts gene expression, protein turnover, metabolism, external signalling molecules, and many other things. Of course, this is a two-way street, as cells also affect their surroundings (4).

In this regard, cancer cells are no different. They do not exist independently of the body that surrounds them. In fact, cells of solid tumours have been shown to actively manipulate their surroundings to their advantage, creating something called the tumour microenvironment (5).

Given how different the environments between the two types are, it wouldn't be a far stretch to propose that such a different environment may influence how the cancer cells behave. To a certain extent this is true. However, the uncontrolled growth that leads to these tumours actually happens under very similar conditions.

The way solid tumours grow, is likely the easier of the two to understand. In solid tumours, the cancer cells divide inside of the cohesive mass. Generally, they divide and give rise to two equal descendant cells that remain inside the tumour. Basically, these are clones of the previous cancer cells, and they retain the ability to divide. For the purpose of growth, we now have two new cancer cells, where we before had one. Over time, the "production capacity" of the cancer increases as more cells accumulate, which leads to exponential growth.

Liquid tumours are slightly different. Much like the solid tumour, the uncontrolled growth occurs within a solid context. Usually, these are haematopoietic or lymphatic organs, such as the thymus, the bone marrow or lymph nodes, all of which are cohesive organs. However, unlike the solid tumours, they do not divide into two equal descendants and instead follow a hierarchical organisation (6).

Normally, the precursor cell will divide into a new precursor cell and a differentiated cell. The new precursor cell behaves similarly to the cells of a solid tumour. It remains in the solid context and retains the ability do divide into new cells. The difference is the differentiated cell, which will leave the solid niche and enter circulation in the blood and lymphatic system, forming the liquid tumour of such a cancer.

Normally, these circulating cells also lose all of their proliferative capacity. Even in cases where they retain the ability to proliferate, the circulating cells will do so at much lower rates, which means they contribute little to the accumulation of cells. The "productive capacity" of such liquid tumours remains constant, as no new "producer cells" are created, which leads to linear growth instead of exponential.

Of course, since we are dealing with biology, this division into symmetrical and asymmetrical proliferation isn't always true. It is much closer to a tendency than a global rule that all solid and liquid tumour cells follow. Some cells of liquid tumour perform symmetrical division and give rise to two equal descendant, whilst some solid tumour cells divide asymmetrically and give rise to two different cells (7, 8).

Curiously, whilst the growth of liquid tumour occurs within a solid context, cells from solid tumours can also enter into circulation. This is the case with metastases, where cancer cells will detach from the solid tumour and enter circulation, eventually settling down somewhere else in the body to create another solid tumour.

The interesting part it that, whilst in circulation, these metastatic cells significantly reduce, or completely stop proliferating, even though they are usually highly proliferative in a solid context (9). This behaviour is similar to liquid tumour cells only dividing in a solid context, but not in circulation.

Thus, the uncontrolled growth of both liquid and solid tumours occurs only in a solid context (10).

That means, if the growth inside of these solid niches is stopped or reversed, cancer progression can be halted or reversed as well, regardless of whether the cancer manifests as a liquid or solid tumour. Furthermore, the conditions inside of these solid niches, as well as the metabolic state of the cells found therein, don't differ significantly between the two types of tumours (11, 12, 13, 14, 15). This enables us to use the same remedies for liquid tumours that we might use for solid tumours, such as alkalisation, a ketogenic diet, lowering inflammation and others.

I won't go into the details of these remedies in this article, as the focus was the differences and significant similarities between solid and liquid tumours, but you can find more information about them in other articles we've written (the keywords above include hyperlinks to some of them).

Liquid and Solid Tumours

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References:

1. https://www.thermofisher.com/de/de/home/life-science/cancer-research/solid-tumor-research.html
2. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/solid-tumor
3. https://www.rogelcancercenter.org/blood-cancer/overview-leukemia-and-lymphoma
4. Bloom AB, Zaman MH. Influence of the microenvironment on cell fate determination and migration. Physiol Genomics. 2014 May 1;46(9):309-14. doi: 10.1152/physiolgenomics.00170.2013. Epub 2014 Mar 11. PMID: 24619520; PMCID: PMC4035623.
5. Bożyk, A.A.-O., Wojas-Krawczyk, K.A.-O., Krawczyk, P., and Milanowski, J. Tumor Microenvironment-A Short Review of Cellular and Interaction Diversity. LID - 10.3390/biology11060929 [doi] LID - 929.
6. Chennamadhavuni A, Iyengar V, Mukkamalla SKR, et al. Leukemia. [Updated 2023 Jan 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560490/
7. Dingli D, Traulsen A, Michor F (2007) (A)Symmetric Stem Cell Replication and Cancer. PLoS Comput Biol 3(3): e53. https://doi.org/10.1371/journal.pcbi.0030053
8. Majumdar S, Liu ST. Cell division symmetry control and cancer stem cells. AIMS Mol Sci. 2020;7(2):82-98. doi: 10.3934/molsci.2020006. Epub 2020 May 6. PMID: 32953979; PMCID: PMC7500705.
9. Kohrman AQ, Matus DQ. Divide or Conquer: Cell Cycle Regulation of Invasive Behavior. Trends Cell Biol. 2017 Jan;27(1):12-25. doi: 10.1016/j.tcb.2016.08.003. Epub 2016 Sep 12. PMID: 27634432; PMCID: PMC5186408.
10. Mian, S.A., Ngo, S. & Bonnet, D. Is the bone marrow microenvironment the hidden catalyst in malignant haematopoiesis?. Leukemia 39, 1589–1592 (2025). https://doi.org/10.1038/s41375-025-02630-6
11. Li Y, Patel SP, Roszik J, Qin Y. Hypoxia-Driven Immunosuppressive Metabolites in the Tumor Microenvironment: New Approaches for Combinational Immunotherapy. Front Immunol. 2018 Jul 16;9:1591. doi: 10.3389/fimmu.2018.01591. PMID: 30061885; PMCID: PMC6054965.
12. Tjahjono E, Daneman MR, Meika B, Revtovich AV, Kirienko NV. Mitochondrial abnormalities as a target of intervention in acute myeloid leukemia. Front Oncol. 2025 Jan 20;14:1532857. doi: 10.3389/fonc.2024.1532857. PMID: 39902131; PMCID: PMC11788353.
13. Zhang, A., Liu, W., and Qiu, S. (2024). Mitochondrial genetic variations in leukemia: a comprehensive overview. Blood Science 06, 225-229. 10.1097/BS9.0000000000000205.
14. Panina, S.B., Pei, J., and Kirienko, N.V. (2021). Mitochondrial metabolism as a target for acute myeloid leukemia treatment. Cancer & Metabolism 9, 17. 10.1186/s40170-021-00253-w.
15. Czegle I, Gray AL, Wang M, Liu Y, Wang J, Wappler-Guzzetta EA. Mitochondria and Their Relationship with Common Genetic Abnormalities in Hematologic Malignancies. Life (Basel). 2021 Dec 7;11(12):1351. doi: 10.3390/life11121351. PMID: 34947882; PMCID: PMC8707674.