choice of cell line for orthotopic xenograft implant - (Aug/15/2012 )

Hi,

I don't have any experience in developing an orthotopic mouse model but will have to work with one soon.

I have a few queries and any help/advice would be much appreciated.

I have to develop a colorectal cancer orthotopic mouse model. I understand there are two ways.
A. inject cell suspension into the cecal wall and

B. implant pieces of subcutaneous tumor into the cecum. I've read that injection of cell suspension does not result in metastasis. Anyways, how do I check which mouse models are compatible with which cell line. Also are nude mice used for xenograft implanted orthotopic models? BALB c or BALB c nu/nu mice ?

For most subcutaneous and orthotopic tumor model, you need immunocomprimised mice to support tumor growth. nu/nu nude mice are just one type of them.

As you mentioned, injecting cell suspension or tumor tissues (from subcutaneous tumor or human tumor) are both widely used depending on tumor site. For example, cell suspension and tumor pieces have been used to establish orthotopic prostate cancer in mice.

Thank you. Can I ask what does it imply by mice strain being in synegic with cell lines? For an orthotopic mouse model, is it mportant to use cell lines which are in synegic with the mouse strain. Or can we use human derived cancer cell lines for an orthotopic mouse model? I'm sorry if these questions sound silly. I just don't have any experience in developing cancer mouse models.

If you want to use/study the growth of tumors of human origin, then you need to use immunocompromised mice. The reason being that such mice cannot immunologically reject the foreign (i.e. non-mouse) tissue. The disadvantage of such a model is that you are investigating tumor growth (or perhaps an agent that can suppress tumor growth) in an animal that does not have a competent immune system. To overcome this disadvantage, you could use a syngeneic tumor model. In this kind of model, cancer cells or tumor fragments of mouse origin are injected/implanted into a mouse. The murine tumor fragment or cancer cells should come from a mouse of the same strain (i.e. syngeneic) as that into which you are introducing the cancer cells/tissues. This will prevent immunologic rejection based on strain differences. Thus, the advantage of this syngeneic model is that you can study the tumor in the context of an intact immune system. Also, immunocompetent mice are often less expensive than immunocompromised mice. The disadvantage is that it is a mouse tumor, not a human tumor.

Hope that helps.