The tumor stroma represents the supportive tissue surrounding and intermingled with cancer cells. This complex environment plays a significant role in cancer development, influencing how tumors grow, spread, and respond to treatments. Understanding the tumor stroma is reshaping how researchers approach cancer therapies, moving beyond just targeting the cancer cells.
What is Tumor Stroma
The tumor stroma is the non-cancerous environment found within a tumor. It functions as a complex ecosystem, providing the necessary “soil” and “scaffolding” for tumor cells to thrive. The stroma is a dynamic tissue that actively participates in tumor progression.
Every solid tumor possesses stroma, which is required for the tumor to grow beyond a minimal size. This supportive environment is largely a product of the host’s normal tissues, induced through interactions with tumor cells. The stroma’s composition can vary considerably between different cancer types.
Key Components of the Tumor Stroma
The tumor stroma is a complex network composed of various cell types and non-cellular elements. Among the cellular components are cancer-associated fibroblasts (CAFs), which are activated fibroblasts that contribute to the stroma. These cells can stimulate cancer cell growth and invasion.
Immune cells are also abundant within the stroma, including macrophages, lymphocytes, and neutrophils. These immune cells can have multifaceted roles, either promoting or inhibiting tumor development. Endothelial cells are another cellular component, forming new blood vessels that supply the growing tumor with nutrients and oxygen.
Beyond the cells, the extracellular matrix (ECM) forms a major part of the tumor stroma, providing structural support and influencing cellular behavior. The ECM includes various proteins such as collagen, elastin, fibronectin, and laminin. Proteoglycans and glycosaminoglycans are also present.
How Stroma Influences Tumor Behavior
The tumor stroma influences cancer progression through various interactions. It provides physical support, acting as a scaffold that helps maintain the tumor’s structure as it grows. This structural integrity allows tumor cells to organize and expand.
The stroma also supplies nutrients and growth factors that fuel tumor cell proliferation. Cancer cells secrete factors that activate and recruit stromal cells, creating a reciprocal relationship that promotes tumor growth. This communication involves paracrine signaling, where tumor cells release substances like growth factors, cytokines, and chemokines that attract and activate stromal cells, which then produce factors that aid tumor progression.
Angiogenesis, the formation of new blood vessels, is largely driven by the tumor stroma. Endothelial cells within the stroma develop new vasculature, essential for delivering oxygen and nutrients to the expanding tumor mass and for removing waste products. This newly formed vascular system also provides pathways for cancer cells to escape the primary tumor.
The stroma modulates the immune response within the tumor microenvironment, creating an immunosuppressive environment. This allows cancer cells to evade detection and destruction by the body’s immune system. For instance, certain immune cells within the stroma can suppress anti-tumor immunity, hindering the effectiveness of the body’s natural defenses against cancer.
The tumor stroma also facilitates metastasis, the spread of cancer cells to distant sites. The altered extracellular matrix and the presence of specific stromal cells can create pathways and conditions that promote the migration and invasion of cancer cells. It also contributes to drug resistance, as the stroma can act as a physical barrier to drug delivery and provide signals that protect cancer cells from therapies.
Targeting the Tumor Stroma
Understanding the role of the tumor stroma has opened new avenues for cancer therapy. Researchers are developing strategies to target specific components of the stroma, aiming to disrupt the supportive environment that allows tumors to thrive. This approach can enhance the effectiveness of conventional cancer treatments.
One approach involves inhibiting angiogenesis, thereby cutting off the tumor’s blood supply and starving it of essential nutrients. Another strategy focuses on reprogramming cancer-associated fibroblasts (CAFs). Since CAFs contribute to tumor growth, drug resistance, and immune suppression, modifying their behavior could weaken the tumor’s support system.
Enhancing immune cell function within the stroma is also being explored. By overcoming the immunosuppressive environment created by the stroma, therapies can help the body’s immune system more effectively attack cancer cells. For example, targeting proteins like periostin can decrease immune-suppressive macrophages and increase T cells in the tumor microenvironment, making “cold” tumors more susceptible to immune attack. These stromal-targeting strategies are often combined with existing treatments, aiming for a more comprehensive attack on cancer.