A Short Overview of Tumor Spheroids as a Subject of Tumor Research

Luidmila N Komarova; Alina K Lapenko; Marina I Klinovitskaia

doi:10.37871/jbres1987

ISSN: 2766-2276

Biology Group. 2024 August 31;5(8):1057-1059. doi: 10.37871/jbres1987.

Subject area(s)

Biomedicine
Molecular Biology

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Editorial

A Short Overview of Tumor Spheroids as a Subject of Tumor Research

Luidmila N Komarova*, Alina K Lapenko and Marina I Klinovitskaia

Obninsk Institute for Nuclear Power Engineering, National Research Nuclear University MEPhI, Obninsk, Russia

*Corresponding authors: Luidmila N Komarova, Obninsk Institute for Nuclear Power Engineering, National Research Nuclear University MEPhI, Studgorodok 1, Obninsk, Kaluga region, 249039, Russia E-mail:

Received: 30 August 2024 | Accepted: 30 August 2024 | Published: 31 August 2024

How to cite this article: Komarova LN, Lapenko AK, Klinovitskaia MI. A Short Overview of Tumor Spheroids as a Subject of Tumor Research. J Biomed Res Environ Sci. 2024 Aug 31; 5(8): 1057-1059. doi: 10.37871/jbres1951, Article ID: jbres1757

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Cancer is a common disease. The action of cancer-causing factors occurs at the molecular level and is based on intracellular interactions that take place within a complex heterogeneous tumor environment [1]. The tumor micro environment comprises non-cancerous cells, including endothelial cells, fibroblasts, cells of innate and adaptive immunity, as well as non-cellular components such as chemokines, cytokines, and growth factors [2,3]. These intricate and interdependent interactions have a significant impact on the efficacy of tumor disease treatment when drugs are used in clinical settings [4]. Furthermore, the tumor cell population is heterogeneous in terms of proliferation rate, nutrient and oxygen concentration and accumulation of metabolic products [5]. These tumor properties impede accurate prediction of the effects of treatments such as radiotherapy and chemotherapy [6]. This highlights the necessity for preclinical models that accurately describe tumor properties. Tumor spheroids, which are three-dimensional cell structures comprising one or more cell types, meet this criterion [7]. The advantage of this cell model is that it allows to reflect inter- and intracellular interaction in a volume that closely resembles the physiological state of the organism.

Tumor spheroids are formed through the creation of an extracellular matrix environment by cells which synthesized and accumulated an extracellular matrix. It is a non-cellular component that serves to mold the environment of cells and mediate their interactions. The extracellular matrix is primarily composed of proteins, including collagen, proteoglycans, fibronectin, and integrins. It has been demonstrated that the extracellular matrix plays a pivotal role in regulating the proliferation, differentiation, and response of cell populations to external factors, such as chemotherapy and ionizing radiation. The use of agarose in the extracellular matrix is especially promising. Due to its status as a natural polysaccharide polymer with excellent biocompatibility, agarose has tunable mechanical properties, low cost, and thermally reversible gelation [8]. In this context, the development of three-dimensional cell spheroids using agarose in conjunction with collagen, a key component of the extracellular matrix, is a significant advancement in three-dimensional cell cultivation [9].

To date, a number of methods have been developed for the creation of tumor spheroids. One approach is based on the creation of a non-adhesive system [10]. This technique allow to create conditions that facilitate the self-assembly of cancer cells into a three-dimensional aggregate. Also relevant methods are the use of rotary and microfluidic facilities [11,12]. These methods have been demonstrated to be effective, applicable, and the possibility of further improvement. Furthermore, the creation of three-dimensional cell cultures has been successfully achieved through the use of biomaterials derived from a variety of sources [13]. A biomaterial can be defined as a substance or combination of substances of natural or synthetic origin that is capable of partially or completely replacing other substances and modifying the characteristics of biological object. Biomaterials can be classified into three main categories: natural polymers (e.g. chitosan, alginate, hyaluronic acid), peptides (e.g. collagen or gelatin) and synthetic polymers (e.g. polyethylene glycol, poly (lactic acid), poly(lactic-glycolic acid), etc.). Matrices based on the listed biomaterials are widely used in the formation of tumor spheroids.

The composition of spheroids is typically classified into two main categories: homogeneous and heterogeneous systems. Homogeneous systems are formed through the aggregation of a single cell line and indicate exclusively its proliferative potential. In contrast, heterogeneous systems are formed through the co-culturing of tumor cells with stromal fibroblasts, endothelial cells, mesenchymal stem cells, and immune system cells [14].

In order to ensure the reproducibility and reliability of experiments conducted on three-dimensional cell cultures, it is essential to obtain tumor spheroids comply with a number of pre-defined indicators. These parameters include the shape, diameter, and volume of the spheres formed [15]. The evaluation of the properties of three-dimensional cell cultures allows the formation of spheroids that are specifically tailored to meet the requirements of a given task [16].

The size of the tumor spheroids formed may influence the sensitivity of the therapeutic agents. A study conducted on glioblastoma cell lines demonstrated that large spheroids, exceeding 400 µm in diameter, showed a larger necrotic core in comparison to smaller spheroids. Among others, this phenomenon affects the absorption of a range of agents and drugs. Therefore, it is essential to optimize the size of the spheroids in accordance with the study protocol. One of the most fundamental and straightforward methods for controlling the size of a tumor spheroid is to alter the cell seeding density. For instance, seeding 3000 cells with a diameter of 560 ± 30 μm resulted in the optimal concentration for the formation of spheroids from HCT116 colorectal cancer cell line to study metabolom [17]. A study conducted on cell lines of malignant pleural mesothelioma and lung cancer demonstrated that seeding 1000 cells per spheroid was sufficient to form a spheroid with a diameter of 100 μm [18].

In practice, three-dimensional cell models of tumors are used in the study of the effects of modern antitumor agents. For example, a three-dimensional cell model of an ovarian adenocarcinoma tumor spheroid has been studied under the action of photodynamic therapy and photosensitizers. Despite extensive exposure to photodynamic therapy, tumor spheroids demonstrate enhanced survival rates relative to monolayer cultures. The complex structure of the cell aggregates restricts the penetration of the photosensitizer to deeply embedded cells, which may result in a change in the therapeutic efficacy observed in monolayer studies and three-dimensional cell cultures [19].

Tumor spheroids may serve as a bridge between preclinical and clinical research, since they represent a universal model of malignancy in the body. Currently, methods for developing a platform for assessing the effectiveness of drugs based on tumor spheroids are being actively improved, as this can potentially provide new knowledge about cancer therapy.