The growth factor demands of several tumor cells are diminished in comparison to their normal counterparts,

hence facilitating the uncontrolled multiplication of tumor cells both in laboratory settings and inside living
organisms. In some instances, cancer cells have the ability to generate growth factors that facilitate their own
proliferation (Figure 15.9). The excessive secretion of a growth factor by a responsive cell results in persistent
self-stimulation of cellular proliferation (autocrine growth stimulation), hence reducing the reliance of cancer
cells on growth factors derived from other, physiologically typical sources. In certain instances, the diminished
reliance of cancer cells on growth factors can be attributed to irregularities within intracellular signaling
mechanisms. These irregularities may manifest as uncontrolled activation of growth factor receptors or other
proteins, such as Ras proteins or protein kinases, which were previously examined in Chapter 13 as constituents
of signal transduction pathways that facilitate cellular proliferation.

In Figure 15.9, the concept of autocrine growth stimulation is shown.

In Figure 15.9, the concept of autocrine growth stimulation is shown. A cellular entity synthesizes a growth
factor that elicits a response from the same cell, hence leading to persistent stimulation of cellular proliferation.

Cancer cells have a reduced level of regulation compared to normal cells with regards to interactions between
cell-cell and cell-matrix. The sticky properties of most cancer cells are often less compared to those of normal
cells, mostly due to a decrease in the expression of cell surface adhesion molecules. One significant factor in the
progression of carcinomas, which are a kind of epithelial cancer, is the loss of E-cadherin, a key adhesion
protein found in epithelial cells. The diminished production of cell adhesion molecules leads to a decreased level
of contact between cancer cells and other cells and tissue components. Consequently, this facilitates the invasive
and metastatic capabilities of malignant cells. The diminished adhesive properties of cancer cells give rise to
changes in both their morphology and cytoskeletal structure. Numerous tumor cells have a more spherical
morphology compared to their normal counterparts, mostly due to reduced adhesion to both the extracellular
matrix and adjacent cells.

The phenomena of contact inhibition (Figure 15.10) serves as a clear demonstration of the contrasting cell-cell
interactions seen between normal cells and cancer cells. Fibroblasts in their normal state exhibit migratory
behavior as they traverse the surface of a culture dish until they establish contact with an adjacent cell.
Subsequently, the process of cell migration is impeded, leading to the adherence of normal cells to one another,
resulting in the formation of a well-organized arrangement of cells on the surface of the culture plate. In
contrast, tumor cells have a distinct behavior wherein they persist in their movement even after coming into
touch with neighboring cells. They have the ability to migrate across adjacent cells and proliferate in
disorganized, multilayered arrangements. Cell-cell contact not only inhibits the mobility of cells, but also
hinders the proliferation of several normal cells. In contrast, cancer cells exhibit a distinct insensitivity to this
growth inhibition caused by contact with neighboring cells.

In Figure 15.10, the concept of contact inhibition is shown.

In Figure 15.10, the phenomenon of contact inhibition is shown. The provided images are light micrographs (on
the left) and scanning electron micrographs (on the right) illustrating normal fibroblasts and tumor cells. The
migration of normal fibroblasts is impeded by cellular contact, resulting in the formation of a well-organized,
adjacent arrangement on the surface of (more...).

There are two supplementary characteristics shown by cancer cells that significantly influence their interactions
with other components of tissue, thus playing pivotal roles in the processes of invasion and metastasis. Initially,
it is common for malignant cells to release proteases that facilitate the degradation of extracellular matrix
components. This enzymatic activity enables cancer cells to infiltrate neighboring normal tissues. The secretion
of collagenase is considered a crucial factor in the capacity of carcinomas to degrade and infiltrate basal
laminae, hence facilitating the invasion of underlying connective tissue (refer to Figure 15.5). Additionally, it
should be noted that cancer cells have the ability to generate growth factors that facilitate the process of
angiogenesis, which is the production of new blood vessels. The process of angiogenesis is essential for
facilitating the expansion of a tumor over a certain threshold of around one million cells. At this critical stage,
the development of new blood vessels becomes necessary to sustain the provision of oxygen and nutrients to the
rapidly multiplying tumor cells. The formation of these blood vessels is a consequence of the presence of
growth factors, which are released by the tumor cells. These growth factors encourage the proliferation of
endothelial cells located in the walls of capillaries in the adjacent tissue. Consequently, new capillaries extend
into the tumor, leading to its expansion. The development of these novel blood arteries has significance not only
in facilitating the growth of tumors, but also in enabling the spread of cancer cells to distant sites. The newly
created capillaries that are actively forming in response to angiogenic stimulation are susceptible to infiltration
by tumor cells, therefore facilitating their entry into the circulatory system and initiating the metastatic cascade.