Not all tumor cell lines will grow as an allogeneic model. In general only the more aggressive tumors can out grow host immunity. Immune deficient mice can be used to address the role of specific immune cells with allogeneic tumor or for studies using xeongraft tumors. Some tumor cell lines were initiated prior to the development of in-bred mice and so are grown as an allo-model. As discussed above, results using tumors in out-bred hosts are less reproducible and overall it is best to use immune intact mice and allogeneic tumors only to address alloantigen question. As an editor-in-chief we normally initiate an editorial rejection of any paper using out-bred mice and tumors due to the potential lack of reproducibility.

It is possible to establish tumour models in outbred mice using cell lines but your results may not be as consistent and reproducible as those yielded from inbred animals.

I agree with Farbod. You can induce tumor on both inbred mice and outbred mice, and can compare the outcomes. Inbred mice give more reliable results compared to outbred mice and at the end of the day, you will observe that results of inbred mice are more reproducible and evaluation of a particular drug on the tumor induced mice (inbred), could yield better and reliable results.

Sure.. We use both inbred and outbred stains and it works equally good with the tumor induction.. Just make sure that they are immun-compromised to accept those cells.

Some tumors can grow across MHC barrier, for example, Ehrlich ascites carcinoma. Nevertheles, I flatly recommend NOT to use outbred animals in experiments with transplantation of tumor cells. Otherwise, results will be unpredictable and uninterpretable. I have severe doubts that any reputable journal will publish them.

Not all tumor cell lines will grow as an allogeneic model. In general only the more aggressive tumors can out grow host immunity. Immune deficient mice can be used to address the role of specific immune cells with allogeneic tumor or for studies using xeongraft tumors. Some tumor cell lines were initiated prior to the development of in-bred mice and so are grown as an allo-model. As discussed above, results using tumors in out-bred hosts are less reproducible and overall it is best to use immune intact mice and allogeneic tumors only to address alloantigen question. As an editor-in-chief we normally initiate an editorial rejection of any paper using out-bred mice and tumors due to the potential lack of reproducibility.

I would certainly go in the same direction as James. The best is to use inbred mice. During the last 20 years of research in our institution (Transgene Biotech Company, Strasbourg France), we never employed outbred mice for syngeneic or xenogenic murine experiments.

The answer really depends on what question you're trying to answer. If you want to establish an in vivo tumor model to study tumor growth or to study the immune system's response to something approximating a "real" tumor, then outbred mice would not be appropriate because the tumor is likely to express alloantigens. Thus, the resulting model would be more akin to an allogeneic transplant model (transplanting tissues from one individual to a genetically distinct individual). Allogeneic transplants are generally vigorously rejected, so your results will muddle transplant rejection and whatever else you are studying. Isogeneic transplantable tumors may also elicit an immune response but that could be something that frequently happens. As you are probably aware, researchers have been studying such systems for nearly a century in an effort to understand, and eventually harness, the body's ability to fight its own tumors.

Invasive tumor cell lines could grow in out bread mice. But after tumor induction, tumor will be rejected spontaneously and will not show real out come of most studies. As mentioned above, journals will not accept articles with out bread tumor mice modeling.

Talmadge and Netzer have given good answers. My question to you is why use outbred mice? Is it not possible to get the correct inbred strain? Is the tumour itself derived from an outbred animal? The most aggressive tumours frequently down-regulate their histocompatibility antigens and can grow across MHC barriers. However the host response will be heterogeneous and not reproducible from animal to animal. If you don't aim to publish, there are still interesting experiments you could do. However much tumour biology research has been done in the past century - inbred, outbred and immunodeficient. Search PubMed first.

Not all tumor cell lines will grow in outbred mic.Nude mouse will help growing and tumor cell lines.-P.K.Ray

All conditions of experiments with transplantable tumor cells must be carefully controlled as much as possible. Evidently, this is impossible in experiments on outbred mice with mixed genetical background. This is also impossible in experiments with tumors that originated from outbred mice. Difference in MHC and minor histocompatibility antigens hardly affects outcome of tumor transplantation, resulting either to complete elimination of tumor cells or to artificial pressure of immune system provoking their fast immune selection in the host. The difference in single product of MHC can resut in complete elimination of tumor cells with subsequent indefinite survival of mice. We see this picture after grafting of EL4 (H-2b) cells to mice of MHC congenic recombinat B10.D2(R101) (KdIdDb) strain. T lymphoma EL4 does not express MHC class II molecules. Therefore. in this system immune response is targeted specifically to H-2Kb molecule. Host CD8 T cells mount robust CTL response resulting to complete elimination of EL4 cells in two weeks and formation of CD8 memory cells, specific to Kb molecule. Then, we modified this experimental system by entry of single transgene of TCR beta chain into R101 mice. This transgene results in formation of repertoire in which 80% of T cells express invariant beta-chain. Then, instead of a full elimination of tumor cells as in wild-type mice, a reproducible prolonged equilibrium phase and subsequent escape was observed in transgenic mice that resulted in death of 90% of the mice in 40-60 days after grafting. Prolonged exposure of tumor cells to the pressure of the immune system in transgenic mice in vivo resulted in a stable loss of H-2Kb molecule on the EL4 cell surface. So, in this allogeneic transgenic model we could see classic pattern of interactions between tumor cells and the immune system, usually observed in reliable syngeneic models of anti-tumor immunity. Finally, I think that there is no considerable gap between recognition of tumor antigens and alloantigens. However, it is evident that all steps in development of models in cancer immunology must be carefully controlled.

Outbread mice? Difficult! (as many already pointed out) I know from my own experience that a single antigen (in otherwise immuno-identical cells) is sufficient to prevent (otherwise pretty agressive) murine leukemia cells from engrafting. That antigen was a retrovirally introduced cytokine receptor subunit, an activated mutant of the human beta common chain (CDw131, in FVB background, beyond this single receptor molecule, the cells came from the identical strain (FVB-derived), While I am not sure about solid tumors (where immune rejection may not be as effective as in Leukemias), what solved the problem for us back then was to irradiate the recipients with a sublethal dose (3Gy). This will suppress the immune system to a level where the cells can engraft. Not sure if this will work with outbread mice, which will have a pronounced MHC-incompatibility to an unpredictable degree. If you have no access to an irradiator, I could imagine that pharmacological ablation of the bone marrow, for instance using 5-FU, might do the trick too. Just transplanting I would be very sceptical that you will get anything else but transplant rejection. Important, when doing such experiments is to keep the recipients under antibiotics as a precautonary measure against infections, for at least two to three weeks after ablation. Its a bit of a gamble and unless you have a very specific reason to use outbread, I would recommend to find different ways to answer your question. You may be spending a lot of time, energy, money and mice on a project with uncertain outcome (reproducibility! as pointed out by several others above like with humans its hard to find two outbread mice with a similar MHC haplotype, even then interpreting your data would be a mess. then to reproduvce, you will never finsd an immunocompatible outbread mouse anymore.). To grow human (or any mouse-strain)- samples in immunodeficient mice, I highly recommend NSG-mice (Shultz et al J: Immunol 174(10) p6477-89, Handgretinger-lab), which are currently considered the state-of-the art model for xenotransplants. They should be commercially available, however will need a clean animal facility due to their immunodeficient nature. OK now, hope, this was helpful!

Cheers to Tehran, Thomas :-)

Thanks All friends. Your answers were entirely helpful. But I think if a drug or any treatment is supposed to work against cancer in human, the term inbred dose not have sense. I know that in experimental model it is needed to reproduce the results and robust results will certainly achieved by inbred mice and I know that you all are indicating to induction of tumor that would be more reliable in inbred mice but I'm trying to find a more closed model o human cancer. As you know in human population similarity in HLA or any other genetic background in cancer treatment is not addressed.

Thank you again for your kind responses

that's because autonomously rising cancerous tissue in humans, has the same genetic background as the normal tissues, hence, same type of HLA molecules, antigens, etc. otherwise immune system wouldn't have had so much difficulty dealing with cancer.

There are many reasons to use outbred mice in immune and cancer studies. Humans are rarely inbred and variability is inherent to clinical studies. However, the study of transplantable tumor in other than a syngeneic system as discussed previously should be avoided. However, that does not mean that autochthonous tumor in an outbred strain are not appropriate. Indeed, spontaneously occurring tumors and chemical, viral, or physical carcinogen-induced tumors are believed to model human tumors more closely than transplanted tumors. Advantages include orthotopic growth, tumor histology devoid of transplantation introduced changes, and metastasis developing via lymphatic and vascular vessels surrounding and within the primary tumor. Autochthonous tumor models have an inherent variability in the time to and frequency of tumor induction, number of tumor(s) induced, and thus the number of animals required for a study. In contrast to most transplantable tumor studies, results in autochthonous tumor studies and clinical meta analyses have suggested that in some instances these tumor models can be predictive for human therapeutic and chemopreventive activity. Am J Pathol. 2007 March; 170(3): 793–804 and any of a number of other papers may be of interest.

James is absolutely right that autochthonous tumors are the most adequate in the studies of tumor biology. The most persuasive classical work by Prehn and Main demonstrating the existence of antitumor immunity used this approach. The greatest shortcoming of these models is uniqueness of spontaneously emergent or carcinogen-induced tumors. As a rule, this uniqueness is hardly compatible with the interests of immunologists, who want to identify antigen, to show effector mechanisms of antitumor immunity, to stimulate this immunity, and, then, successfully vaccinate tumor bearing animals. Transplantable tumors allow to do it much easier. So, I think, only wide combination of different approaches to the studies of tumor immunology will result in success.

Dmitry, excellent comment!

I was trying to make the point that if you really want to use an outbred system this is (to my mind) the only way to do it. As an immunologist/oncologist I use autochthonous tumors in an inbred system as it provides the most rigorous model. Of course it is a very painful (long time) model. Your comment that one should use a combination of different approach is critical. The Am J of Path review that was referenced (attached) reviews most types of tumor models discussing strengths and weaknesses.

Thank you very much, James! As for me, I was not intended to use outbred animals by any mean. My specific scope is to see clear borders between "allo", "tumor" and self, looking from the side of T lymphocytes. Thank you for very interesting reading! Best wishes! Good luck!

This complicate but if you want to induce cancer, this increase with inject of streptozotosin (whose induce diabetes). e.g.

http://www.ncbi.nlm.nih.gov/pubmed/12125095