Fibroblasts and Their Role in Cancer

These flashcards cover the critical concepts regarding fibroblasts' roles in wound healing and cancer according to the lecture notes.

What are fibroblasts and what is their primary function in the human body?

Fibroblasts are essential non-immune and non-epithelial cells, predominantly derived from the primitive mesenchyme. Their primary biological function is to maintain tissue integrity through the synthesis and continuous remodeling of the Extracellular Matrix (ECM).

What does the acronym 'CAF' represent in the context of cancer biology?

'CAF' stands for Cancer-Associated Fibroblast. This term specifically refers to the population of activated fibroblasts that reside within the tumor microenvironment and contribute to the progression of the disease.

Identify the scientist who first described fibroblasts and the year of this discovery.

Fibroblasts were first described by the pathologist Rudolf Virchow in the year 1858.

Explain Rudolf Virchow's 'irritation theory' and its significance in oncology.

The irritation theory, proposed by Virchow, suggest that cancer originates at sites of chronic irritation. This theory is significant because it established an early mechanical and biological link between chronic inflammation and the development of cancer.

How is the 'activated' state of a fibroblast characterized during the wound healing process?

During wound healing, fibroblasts transition into an activated state known as myofibroblasts. This state is characterized by a significantly enhanced capacity for migration and proliferation, allowing the cells to respond effectively to biochemical stimuli from the wound environment.

Describe the two-step progression of fibroblast activation into a myofibroblast.

The activation follows a distinct two-step pathway: 1. Proto-myofibroblast stage: The cell develops increased secretory and contractile capabilities. 2. Myofibroblast stage: Stimulated by signals such as TGF-beta, the cell begins expressing \alpha-smooth muscle actin (\alpha-SMA) and high levels of fibrillar collagens.

In what ways do CAFs influence the behavior and environment of cancer cells?

CAFs influence cancer cells through direct and indirect mechanisms: - Directly: They release a variety of cytokines and growth factors that stimulate cancer cell proliferation. - Indirectly: They modify the physical structure and density of the surrounding extracellular matrix (ECM) to facilitate cell movement and invasion.

What is the Senescence Associated Secretory Phenotype (SASP) in CAFs?

SASP (Senescence Associated Secretory Phenotype) describes a state where senescent Cancer-Associated Fibroblasts, despite having lost their ability to undergo cell division (proliferation), continue to be metabolically active and secrete high levels of growth factors and inflammatory mediators.

List the key signaling molecules and pathways responsible for activating fibroblasts within tumors.

Fibroblast activation is driven by several key signals including growth factors like TGF\beta, PDGF, FGF, and EGF, as well as cytokines such as IL-1\beta and IL-6. These molecules typically trigger internal signaling pathways like the SMAD and JAK-STAT pathways.

Detail the role of Cancer-Associated Fibroblasts (CAFs) in tumor initiation and disease progression.

CAFs play a foundational role in tumor initiation and evolution by altering the tumor microenvironment (TME) to favor growth. They promote cancer cell invasion into adjacent tissues and provide biochemical support that ensures the survival and fitness of cancer cells.

How can the targeting of fibroblasts be utilized as a strategy in cancer therapy?

Therapeutic targeting of fibroblasts focuses on disrupting their supporting role in tumors by: 1. Interfering with their activation processes or signaling functions; 2. Reverting activated CAFs back to a quiescent, non-activated state; 3. Depleting the CAF population to collapse the tumor's supportive microenvironment.