Cancer is a complex disease characterized by uncontrolled cell growth and the potential to spread throughout the body. While much attention focuses on cancer cells, their surrounding environment plays a significant role in tumor development and progression. This environment includes the extracellular matrix (ECM), a complex network of molecules that influences how tumors grow, survive, and spread. Understanding the ECM’s involvement is important in cancer research.
Understanding the Extracellular Matrix
The extracellular matrix (ECM) is a non-cellular network of macromolecules and minerals that provides structural and biochemical support to cells in tissues and organs. This network is composed of fibrous proteins like collagen and elastin, along with proteoglycans and glycoproteins such as fibronectin and laminin. Collagen provides tensile strength and structural support to tissues. Elastin allows tissues to stretch and recoil, providing flexibility.
Proteoglycans consist of a core protein linked to glycosaminoglycan chains, forming a gel-like matrix that retains a large amount of water. This property contributes to tissue hydration, lubrication, and shock absorption. Glycoproteins like fibronectin and laminin are integral, connecting cells to collagen fibers and facilitating cell movement and adhesion within the ECM. In healthy tissues, the ECM is highly organized and undergoes remodeling, maintaining tissue homeostasis.
The Matrix’s Role in Cancer Progression
In a cancerous environment, the extracellular matrix undergoes alterations that contribute to tumor growth, survival, and local invasion. The ECM in tumors often becomes stiffer and more disorganized compared to healthy tissue, promoting increased cell proliferation and survival. ECM stiffness can activate signaling pathways that drive uncontrolled cancer cell growth.
The composition of the ECM also changes in tumors, with increased deposition of certain matrix components. These changes promote angiogenesis, the formation of new blood vessels necessary to supply the tumor with nutrients and oxygen. The altered matrix can also protect cancer cells from programmed cell death, making them more resistant to therapies. Physical and chemical cues from the ECM are sensed by cell receptors, influencing cellular proliferation and differentiation.
How the Matrix Aids Cancer Spread
The extracellular matrix plays a role in metastasis, the process by which cancer cells spread from the primary tumor to distant sites. The altered ECM provides pathways and signals that facilitate the detachment of cancer cells from the primary tumor. Cancer cells can then invade surrounding healthy tissues, breaking through the basement membrane.
Once detached, cancer cells navigate through the interstitial matrix, guided by changes in matrix stiffness and composition, to reach blood vessels or lymphatic vessels. This process of entering the circulatory or lymphatic system is known as intravasation. The matrix can also provide survival signals that help cancer cells withstand transit through the bloodstream or lymphatic system. Upon reaching a distant site, the ECM at that location can facilitate extravasation, where cancer cells exit the vessels and establish new tumors.
The Matrix as a Target for Cancer Therapies
Scientists and clinicians are exploring ways to target the extracellular matrix to combat cancer, recognizing its influence on tumor behavior. One therapeutic strategy involves developing drugs that aim to break down specific ECM components, such as collagen, to reduce tumor stiffness and inhibit its growth. This approach can also make tumors more accessible to traditional chemotherapy drugs, allowing them to penetrate the tumor more effectively.
Other approaches focus on reducing ECM stiffness or blocking the interactions between cancer cells and the matrix. Some therapies aim to disrupt the binding of integrins, cell surface receptors that connect cancer cells to the ECM, thereby inhibiting cell migration and invasion. By modifying the ECM, these therapies seek to prevent cancer cells from spreading to distant sites, a major cause of cancer-related deaths. The rationale behind these strategies is to disrupt the supportive and enabling environment that the ECM provides for tumor progression and metastasis.