The term orthotopic originates from the Greek words orthos, meaning “correct,” and topos, meaning “place.” In biology and medicine, it describes something situated in its normal anatomical position. This concept is applied in fields like cancer research and organ transplantation, where the principle of being in the “correct place” governs how scientists study disease and how surgeons restore function.
Orthotopic Models in Cancer Research
In oncology research, an orthotopic model is created when cancerous cells are implanted into the organ from which they originated in a laboratory animal. For example, human pancreatic cancer cells would be surgically placed into the pancreas of an immunodeficient mouse. This approach allows the tumor to grow in its native environment, which provides a more accurate representation of how a human cancer develops and spreads.
The most common non-orthotopic method is the subcutaneous model, where cancer cells are simply injected under the skin of an animal. This technique is simpler, and tumor growth is easily measured with calipers. The subcutaneous space, however, lacks the specific cellular and molecular characteristics of the organ where the cancer would naturally arise. This environmental difference alters a tumor’s behavior, limiting the model’s relevance to human disease.
The superiority of orthotopic models lies in their ability to replicate the tumor microenvironment. This “neighborhood” consists of the organ-specific blood vessels, structural cells like fibroblasts, and various immune cells that tumors interact with. These interactions influence tumor growth rates, the development of a dedicated blood supply (angiogenesis), and the process of metastasis—the spread of cancer to distant sites. For instance, prostate cancer cells grown orthotopically in a mouse’s prostate gland are more likely to metastasize to locations seen in humans compared to the same cells grown under the skin.
Because of this accuracy, orthotopic models are frequently used to study complex cancers like glioblastoma (a type of brain cancer), where the blood-brain barrier is a factor in treatment, as well as lung, liver, and pancreatic cancers. Research using these models provides more reliable data on whether a potential therapy can shrink a tumor and prevent its spread. The insights gained from these models are important for developing more effective cancer treatments.
Orthotopic Organ Transplantation
In surgery, orthotopic organ transplantation is a procedure where a donated organ is placed into the same anatomical location as the original, diseased organ after its removal. This is the standard for most vital organ transplants, including the heart, liver, and lungs, as it aims to restore normal physiological function.
For an organ to work, it must be connected to the body’s major blood vessels and structures in their proper places. A transplanted heart is placed in the chest and attached to the aorta and pulmonary artery to ensure correct blood circulation. Similarly, an orthotopic liver transplant requires connecting the new liver to the recipient’s portal vein and hepatic artery.
This approach contrasts with a heterotopic transplant, where an organ is placed in a different anatomical location. The most common example is a kidney transplant, where surgeons place the donor kidney in the lower abdomen. This location allows easier access to the iliac artery and vein for blood supply, and the ureter can be connected to the nearby bladder.
While heterotopic heart transplants have been performed, they are rare today. In this procedure, the donor heart is placed alongside the recipient’s failing heart as a form of circulatory support. The orthotopic procedure remains the standard for heart transplantation because it more completely replaces the failed organ’s function and leads to better long-term outcomes.
The Biological Importance of Anatomical Location
The applications of the orthotopic principle in cancer research and transplantation highlight a universal biological truth: location is linked to function. The “neighborhood” in which cells and organs reside—their microenvironment—dictates their behavior and ability to perform their designated roles. This context is not passive but an active participant in biological processes.
In cancer, the microenvironment of the original organ provides the specific signals and structural scaffolding that can promote tumor progression. A tumor is not just a mass of cancer cells; it corrupts its local environment to sustain its growth and spread. This is why a cancer cell that metastasizes behaves differently than it did in its original location.
For a transplanted organ, its anatomical position ensures proper integration into the body’s systems. This precise placement allows the organ to receive the correct neural signals, hormonal messages, and blood pressure needed to function as part of a cohesive whole. Ultimately, the concept of “orthotopic” underscores that no cell or organ operates in isolation.