Cancer Tissue Culture in Cancer Biology

Abstract:

The main aim of a biologist who studies tissue culture in cancer biology is to understand the behaviour of the cancer cell in intact organisms, but understanding cancer biology is a major challenge of this century. Major research has been done, which made itself evident that only new tissue culture cancer model, with low complexity and high predictability, will be useful and allow the development of effective therapies. In this article, we are going to discuss the development or advancement of tissue culture engineering, especially how three-dimensional technique is useful in cancer tissue culture. The 3D techniques and new models are helpful in several ways like reproducibility, Tailorable complexities and mainly ethical sustainability which makes suitable tools not only for mimicking tissue regenerations but also for producing many effective therapies which gonna be very useful. Then finally we will be discussing important research and studies which is been recently reported in the public literature about cancer TE. This article will show you a general achievement in cancer biology which is really beneficial in cancer tissue culture.

A special little focus was given to pancreas, breast and prostate tumour. [1]

INTRODUTION:

As we all know tissue culture is a branch of biology in which tissues or cells higher plants and higher animal is been grown artificially in a controlled environment. Despite our body itself develops and evolve in three dimentional environment since the very first embryonic event but we are still studying two dimentional techniques in cancer biology with the help of vitro cell culture. Futher investigations have confirmed that all the cells change their phenotype when they are cultured in 2 dimentional condition. But mostly there results are unsatisfactory. Therefore, there are tremendous need for new 3D model which makes it easy to understand all the biological process at the base of tissue and organ development and also there homeostasis and not to a lesser extent, degeneration and alteration. [2]

Most of the cell biologist still systemically using 2 dimentional model for drug-screening. Cancer cells have the ability to replicate rapidly as they are highly invasive, making their isolation and culture very simple. 2D model have become very assible method for the free preliminary assessment of tumour pharmacotherapy. There are many other model which are used in cancer biology like animal model in which human tumour cell is been injected to form a tumour. This is one of the method which is used in many laborary and requires ethical approval as well. As both the above mentioned models have their own importance but they suffer from important limits which usually nullify the setup of really effective threapies. So intermediate 3D models is being developed and handled by cancer biologist know as spheroids which are mimic only some aspects of tumour biology.

The concept of 3D model and many other newly developed models is very recent, but holds great promise there objective and methologies between both disciplines is been highlted and discussed everywhere.

3 Dimentional Model in Cancer tissue culture

This model have its own individual role in tumour biology which now a days providing very important insights cancer biology and also increasing our understanding for cellular differentiation, tissue organisation and homeostasis which provide a suitable environment for all the cancer research in contrast to complex host environment especially of an in vivo model.

As this 3D culture model have enormous potential it is been currently exploited by many of the branchs of bio medical science so it has become the major focus of research. In todays generation there has been many recent advances in tissue engineering techniques and 3D culture has enabled the great development of heterologous 3D tumour model. Now we are going to discuss about the newly developed tumour model in detail.

Tumour Model: Apprehension versus complications

In the second half of last century the research for cancer biology has been started and it is still going on in progress (Figure 1A). 2D models are traditional in vitro system and also have very appealing advantages to the scientist as they are highly reproducible and responsive to all the drugs and radiations but this model suffer from limited preditibility all because of number of reasons whose deep understanding is still figuring out by scientist so 2D model is basically insufficient all we can say basically it seems to have three main aspects as follow: model dimensionality, cell sources and micro environment complications.

So 3D model or 3D tissue structure are markedly variegated, comprising several cell types and mutual support in over all secretion of specific soluble factor and ECM molecule which also include vascularisation as we have discussed earlier themostwidely3D model is animal model in cancer biology in which vitro selected human cancer cell is been injected by keeping an nude animal as a host and then grown to form tumour masses. As this animal model looks to be very promising but at the end it has poor result this is because of following reason which is as follow:

The immune system of animal sometimes create problem as it is not able to compromised as human cells and became insufficient to be a part of therapeutic screening.

Secondly, the life span of an animal is mostly shorter then the relapse time of human tumour lets consider the example of mice which is generally used as a host animal its life span is very short.

Lastly, the most important factor is tumour micro environment, supporting cell infiltration and vascularisation are of animal origin while the tumour cells are of human origin.

These all reason cause a unsatisfactory and unpredicted response to the therapies so to over come all these problems a newly and advanced model has been developed.

Nevertheless, there are still some side effect has been seen of using animal in study of human diseases, like its effect finance and general lack of predictibility.

In time, in vitromodels of the cancer have been started to evolve towards the third dimension. Simply three dimentional in the vitromodels used by the scientists which includes the formation of spheroids and the gel inserting of the tumour cells . Spheroids are specially the culture artefacts leading, for some of the transformed-cell typeswhich need to an induced cell aggregation in the form of solid spheres with the diameters of ranging from 20–1,000 µm. For the nature of spheroids which partially mimic to the tumour microenvironment as shown : they display secretion of tumour ECM, three dimentional cell-cell interactions, increased chemoresistanceand diffution gradient , while there phenotype diversity is almost missing^.Moreover the spheroid-based assays are generally lack the efficiency due to several problem in there management of the cell aggregation.. With attempting to improve the three dimentional models, also cancer cells have a been inserted in biologic hydrogels, which should copy the primary ECM of the tissues. though, such types of gels usually show unsatisfactory porosity to obtain the long-term cell survival and decent tumour ECM deposition. besides, spatial sharing of cells in the gel is usually not constant, thus resulting in bad rational models.

Figure 1: Systematic picture of tumour model showing its main characterisice which include model-inherent features like reproductibility and model type and also some model biomimetic capability.

Recently the new circuit has been developed called micro fluidics circuit which is making the further new step in 3D culture in cancer, yet it is not achieved as it is suffering from several problem. So to solve these problem or challenges, micro fluid well system is been developed and used with combination of hydrolysisor sometimes it can be used alone.

PancreAS CANCER MODEL

Pancreatic ductal adenocarcinoma (PDAC) ) is the main object of persistent studies due to its inauspicious prognosis. The atimulation of specific PDAC microenviroment by the development of an invitro three dimentional model is still a main goal which is need to be achieved for the development of efficient and effective therapies.In pancreatic model it is found in recent studies that spheroid structures is been embedded in methylecellulose by using cell lines of pancreatic model.The gene expression profiles and the ECM components in the three dimentional model were upregulated, while other selective microribonuclic acids inhibition is enhanced and demonstrated chemoresistance.Hosoya and his colleages has recently reported the gel embedding-like approach. The proposed 3D model is been created on theTranswell® inserts of alternating layers of cell and gelatine-fibronectin , thus they are reproducing some of their basic ECM structural features. This model was been set up to study its diffusion of dextran nanoparticles by using a murine fibroblast cell line which is derived from normal fibroblasts and pancreatic tumour and as controls. Results showed THE decreased permeability of the dextran which is depending on the nanoparticle size and layer number WITH TUMOUR DERIVED CELL also demonstrating a good companionship with the tumour ECM. In this review article, we will be discussing on a some studies, which were reported about the TE approach for PDAC study. Both the groups which are employed scaffolds are completly based on the synthetic polymers, which defines the architecture and the surface morphology so to regenerate the PDAC in the combination with gelatine and to ensure cell adhesion and the growth. In the very first study, the human PDAC (hPDAC) cells,and the PP244, were grown on polyvinyl alcohol (PVA), and also the cell metabolic activity were compared with there obtained in 2D culture controls. The results showed by usable cells, with the enlarged metabolism, in the three dimentional model. The secondly and the most recent study which is used in CSCs is imitative from human pancreatic tumourswhich shows CD24[+]and CD44[+].In this review article , the three dimentional model is displayed on an improved by neoplastic formation, with the tumour volume and the weight higher than those of the two dimentional model.

Fig. 1. pancreatic ductal adenocarcinoma progression model from normal (left) to carcinoma (right). the accumulation of specific genetic alterations is a historical process.

Breast and prostate cancer models

The study of metastasis initiation in three dimentional model have been developed, with the use of cellular spheroids, and all the microfluidic devices. Acknowledge the importance of breast and prostate cancer due to their extinction of metastasis in the bone, three dimentional models are derived from TE know-how, has been refined to study metastatic events of all the cancer types to the bone engineered tissue. The Cancer cell angiogenic signalling are organized by integrin and correlated with enhanced manufacturing of interleukin-8 (IL-8). Further rule over tumour angiogenesis was altered by oxygen availability in three dimentional tumour culture models, with expanded levels of IL-8 excretion in normoxia and of the vascular endothelial growth factor in hypoxic culture circumstances. Alike , porous biomaterials enclosing the inorganic phases like hydroxyapatite (HA) which were used to make initial models of breast metastasis into bones and report a role of HA crystal amount in tumour cell adhesion and reproduction.

Mainly three dimentional systems have displayed that the breast and prostate cancer cells, among others, are indeed more opposing to chemotherapies than when it is cultured on the 2D substratum, thus justifying the go on development of progressivein vitromodels that can repeat not only cell-cell communication but as in current spheroid models, but also in cell-ECM communication. Spheroid and microfluidic culture systems are strained to very tiny artificial surrounding in the order of few hundreds of the microns, which decline to recount the heterogeneouscomplications of bone tissue and prostate metastatic niches. The collective efforts of Hutmacher’s and Clement’s groups have been also demonstrated that the 3D scaffolds can be used to studythe events at the basis of bone metastases, which usually shows the increased invasion of potential and upregulated expression of , steroidogenic enzymes matrix metalloproteases and prostate specific antigen.

Conclusion

There are many pronounced intent sympathy indicating that three dimentional model as a satisfactory development to model cancer tissues. This is a one of the topic of current collective efforts by certain research groups worldwide, whereas, to date, well-defined instruction have not been discussed yet, but still rather preliminary individual studies has been reported. Many studied have shown in every possible ways that three dimentional model is very effective and satisfactory than two dimentional model. The interactions between tumour cells and various different biomaterials seems to play a important key role in tumour biomimetics which is to be finely overburdened in the very near future generation. Many biologist have critised the three dimentional model in cancer biology but some are there in favour of it and still doing research on it.