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Table 1 Overview of similarities and links between biofilm and cancer

From: Immunometabolism in biofilm infection: lessons from cancer

Property Cancer Biofilm
Microenvironment The tumor volume comprises a mixed population of cancerous cells and several local and invading host cells, secretory mediators, and extracellular matrix components, together defined as the tumor microenvironment (Yuan et al. 2016)
The interplay of tumor cells with their environments determines whether the primary tumor is eliminated, metastasizes, or develops latent micrometastases, and these interactions have a significant impact on tumor growth (Yuan et al. 2016)
In parts of the tumor that are proliferating, the surrounding arteries cannot keep up with the increased supply of oxygen, resulting in hypoxic zones inside the tumor and the tumor microenvironment. In order for hypoxia-inducible factors (HIFs) to be digested by the 26S proteasome, prolyl-hydroxylases must mark the HIFs before they are digested. Prolyl-hydroxylases are suppressed in hypoxic circumstances, resulting in the stabilization of HIFs, which in turn stimulates the expression of a variety of genes associated with tumor development and progression (Brassart-Pasco et al. 2020)
The tumor microenvironment is comprised of several biomolecules, such as glycoproteins (fibronectin and laminin), collagens, proteoglycans, and polysaccharides, all of which have distinct physicochemical features (Brassart-Pasco et al. 2020)
A biofilm architecture that has been developed consists of microbial cells and a matrix. It is possible to find noncellular elements in the biofilm matrix as well, relying on the milieu in which the biofilm has evolved. Noncellular elements including mineral crystals, corrosion particles, clay or silt particles, or blood products could be discovered in the biofilm matrix (Donlan 2002)
Notably, current data has shown that bacteria may absorb host components, including fibronectin, mucin, collagen, DNA, hyaluronan, and filamentous polymers, toward their matrix to build a denser biofilm (Walker et al. 2005, Alhede et al. 2020; Birkenhauer et al. 2014; Blanchette and Orihuela 2012)
A steady gradient is established due to the development of the extracellular polymeric material matrix, which provides diverse localized environments on a small scale (Flemming et al. 2021)
Throughout many situations, the biofilm matrix constitutes approximately 90 percent of the overall biofilm volume and is primarily constituted of lipids, polysaccharides, extracellular DNA (eDNA), and proteins, among other things
Genetic changes Anomalous chromosomal numbers are common in cancer cells, and the DNA becomes progressively aberrant due to a plethora of mutations that occur inside them (Cavenee and White 1995)
Some of these alterations are driver mutations, which means that they are fundamental for developing the cell into a malignant oneSeveral malignancies have changed the expression of genes and enzymes involved in DNA and histone modifications, altering the epigenomic landscape throughout tumor initiation and development (Chakravarthi et al. 2016)
Investigations are finding the crucial regulatory functions performed by non-coding RNAs and non-coding elements of the genome during the development of a tumor and those involving protein-coding genes. Many of these genetic and epigenetic changes act in tandem to promote tumor growth and metastasis (Chakravarthi et al. 2016)
It has been hypothesized that the high cell density, enhanced genetic competence, and aggregation of mobile genetic elements that happen in biofilms offer an optimal mix of circumstances for successful horizontal gene transfer, including the absorption of resistance determinants (Flemming et al. 2016)
It is significant to note that the behavior of an organism might influence the quantity and sources of horizontal gene transfer (HGT) that it receives from other organisms. When a bacterium is in a biofilm population, the frequencies of HGT are more significant than when the bacteria is in a planktonic setting (Madsen et al. 2012; Darmon and Leach 2014)
Drug resistance Even while chemotherapy is initially effective against many kinds of cancer, resistance may develop these and other factors, such as metabolic alterations and DNA mutations that enhance drug resistance and degrading
Several aspects of drug resistance in the tumor have been explored, including drug degradation, drug target modification, drug export, DNA damage repair, cell death suppression, and the epithelial-mesenchymal transition (Housman et al. 2014)
The epigenetic alterations that might cause therapeutic resistance were also documented, and it has been hypothesized that such epigenetic variables may result in the establishment of cancer progenitor cells, which seem to be cells that do not die when traditional cancer medicines are administered (Housman et al. 2014)
A number of factors contribute to biofilms' increased antibiotic-tolerance, such as: (i) decreased antimicrobial dissemination or sequestering through the extracellular biofilm matrix; (ii) the occurrence of slow-growing and even latent cells ("persisters") that are highly resistant to antibiotics that address bacterial metabolism; and (iii) the transfer of genetic elements gene encodes resistance determinants as a result of close cell proximity (Flemming et al. 2016; Grassi et al. 2017; Stewart (2015))
Evading the Immune System Tumor cells exert significant attempts to maintain the host's immune response at bay. This includes both the tumor cells themselves, which represent immunomodulatory surface molecules such as PDL1, B7, or human leukocyte antigen (HLA) G, less MHC1 or it is component -2 microglobulin (B2M), and the tumor's microenvironment, which is affected and exploited by the cancer cells (Muenst et al. 2016)
Increased expression of regulatory T-cell populations and consequent anergy of cytotoxic T-cells, interaction with tumor-promoting macrophages (M2 macrophages), and upregulation of the immunosuppression enzyme indoleamine 2,3-dioxygenase (IDO) are all essential factors in the development of tumor (Selvan et al. 2016; Ward-Hartstonge 2017; Prendergast et al. 2017)
TNF-α and TGF-β are secreted by both compartments, as are a variety of other substances like interleukins and interferon. These may both enhance tumor cell survivability on the one side and stimulate the milieu, especially the host immunity, in a pro-tumorigenic way depending on the circumstances (Lippitz 2013, 2018)
Overall, host immunity elicited by a biofilm infection is mainly unsuccessful, resulting in persistent disease. Many research revealed that this happens in many ways, including direct death of leukocytes—macrophages, MDSCs, and neutrophils—or immune reaction regulation (Hanke et al. 2013, Rada et al. 2017)
As shown by the infiltration of MDSCs and macrophage polarization to the anti-inflammatory mode, it has been established that biofilm-derived compounds may effectively reduce pro-inflammatory responses
Persistent biofilm diseases emerge from a failure to develop an efficient immune reaction, requiring physical separation and elimination of infected tissues/medical implants for therapy (Yamada and Kielian 2019)
Communication Tumorigenicity is dependent on the ability of cells to communicate with one another in a healthful milieu. For years, most studies suggested that tumor cells were separated from their neighboring environment and that this lack of cell-to-cell interaction pointed to poor tissue equilibrium and tumor growth and progression. Nevertheless, multiple additional investigations have shown that cell-to-cell interactions were critical in altering the characteristics of the microenvironment in order to generate the tumor niche Eugenin (2019)
The communication between cells, also called cross-talk within the tumor milieu, might be directly through cell-to-cell communication via gap junction crossing, electrical coupling, and adhesion molecules, or secondary by traditional paracrine signaling via cytokines, extracellular vesicles, and growth factors (Dominiak et al. 2020)
Among the most intriguing elements of the bacterial community, life is that it enables bacteria to interact utilizing chemical signals
There is evidence that several of the chemical signals generated by cells and managed to pass through their outer membranes might well be perceived not only by members of the same cell species but further through distinct bacterial communities in the same biofilm population— and possibly even by more complicated organisms in certain instances (Percival 2011)
Microorganisms may interact with one another through quorum sensing during the biofilm-building process. Quorum sensing governs the metabolic reactions of planktonic cells and may lead to the production of microbial biofilms and enhanced pathogenicity (Li and Tian 2012)
Stickiness Healthy cells release chemicals that cause them to adhere to one another in a group. Tumor cells do not produce these chemicals and may "float away" to neighboring places or via the circulation or lymphatic system to distant parts of the body (Coman 1961) Emerging data suggest that biofilm adherence is a significant contributor to biofilm-associated disorders in clinics and biofouling in industrial applications (2021)
As more bacteria aggregate, they begin to produce sticky compounds known as extracellular polymeric components, which they use to encapsulate themselves
Appearance Healthy cells and malignant cells might seem significantly distinct under a microscope. Compared to the normal cells, tumor cells can display substantially more variety in cell size—some are bigger than normal, and others are smaller than normal (2010)
Furthermore, tumor cells frequently have an unusual structure, both in terms of the cell itself and the nucleus (which serves as the "brain" of the cancer cell). It looks that the nucleus is both bigger and darker than that of normal cells (Dey 2010)
Because microbial cells in biofilms are often in close interaction with one another, mechanical connections between surrounding cells are significant (Volfson et al. 2008)
Mechanical instability caused by non—uniform proliferation commonly causes structural alterations throughout an organism's growth. A notable example is the development of 3D wrinkles in bacterial biofilms forming on soft surfaces, improving nutrition and signaling chemical accessibility (Fei et al. 2020)
Chronicity As reported by World Health Organization, cancer has been one of the four most common chronic diseases in the world today (Pizzoli et al. 2019)
Even though cancer can be carefully monitored and managed, it may not always be totally eradicated. It may manifest itself as a chronic (ongoing) condition, similar to diabetes or cardiovascular disease. When it comes to some cancer types, such as ovarian cancer, chronic leukemias, and certain lymphomas, this is often the case (Harley et al. 2012; Markman 2011)
Biofilms have long been recognized as the main cause of most chronic diseases, including osteomyelitis, rhinosinusitis, otitis, diabetic foot ulcers, chronic wounds in general, cystic fibrosis patients' chronic pneumonia, and implants, but are not restricted to these diseases (Kvich et al. 2020)
Metastasis (Spread) One of the last stages of the tumor is metastasis
Many tumor cells lose the adhesion molecules that promote stickiness and can disconnect and migrate via the circulation and lymphatic system to other human body parts (Wittekind and Neid 2005)
Malignant cells enter the circulation or lymphatic system at this step and migrate to a different place in the body, wherein they continue to divide and establish the basis for additional tumors
Although a biofilm is frequently characterized as a "cozy home" in which inhabitant bacteria are sheltered from attack, bacteria may rupture their biofilm connections and escape to colonies other surroundings. This controlled process, known as biofilm dispersion, is found in a broad range of species and is initiated in response to some biological and environmental stimuli (Guilhen et al. 2017)
Treatment method A hallmark of cancer therapy is the combination of two or more medicinal drugs that mainly target cancer-promoting or cell-sustaining processes (Bayat Mokhtari et al. 2017)
Furthermore, combination treatment may be responsible for preventing deleterious impact on cell cells while causing cytotoxic activity on tumor cells. This may happen if one of the drugs in the combined program is cytotoxic to some other medication in normal cells, effectively preserving normal cells against cytotoxic activity (Blagosklonny 2005)
The traditional approach to treating microbial diseases is to tackle the causal pathogens explicitly; nevertheless, the development of biofilms increased the adequate levels of antibiotics to a considerably greater level (Jiang et al. 2020)
Combination treatment is especially promising in the scenario of biofilms because the diverse composition of these microbial populations necessitates targeting cells in various metabolic stages (e.g., actively developing cells and latent cells) (Grassi et al. 2017)