Oncology 9
HC 6
9.1
Organs have well-defined boundaries defined by basement membranes which are acellular
structures made up of extracellular matrix proteins, which keep cells in place. Tumor cells
however compromise this system and are able to metastasize; tumors from a primary site
are able to break free and spread to a distant site. This characteristic feature is only one of
malignant tumors. Metastasis is what makes a cancer lethal, as it interferes with organ
function by physically obstructing or by competing with normal cells for nutrient and
oxygen. It appears though, specific tumors primarily metastasize to certain organs; they
show a preference for an organ, organotropism. This is partially explained by the
directionality of the blood flow, but not always. Cancer cells are like seed and soil; the
metastasizing cells are the seeds, but these require a proper soil to grow. The soil would be
a pre-established niche for the seeds of metastasized tumors to grow. The ability to
metastasize anyway depends on the interactions with cancer cell surface molecules and the
microenvironment (including the ECM). This idea gave rise to the phenomenon of the pre-
metastatic niche. This is a site of future metastasis that is altered to optimally host
metastasized tumor cells in the future. Such an environment is prepared by factors secreted
by the tumor itself, which thus prepare the environment for its arrival.
The metastatic tumor cells from a primary tumor are not clonal, but rather composed of
subpopulations from a genetically identical cells (subclones) differing in mutations due to
evolution. Spreading nevertheless can be monoclonal, seeding by one cell, or polyclonal,
with seeding by multiple subclones. Moreover, the spreading can be linear, one primary
tumor and one metastasis, or branched, with one primary tumor and multiple metastases.
9.2
Metastasis, like carcinogenesis, is a multi-step process on itself. The major steps include
invasion, intravasation, transport, extravasation, and lastly, metastatic colonization.
Additionally, a tumor must not be seen as a clump of proliferating cells, but also the tumor
microenvironment and the tumor-associated stroma is equally important. The metastatic
ability is even determined by the microenvironment.
9.3
The first step of metastasis is invasion. A primary tumor must be able to break free from the
constraints of the local environment and acquire migratory characteristics. This acquisition
or change of the tumor is termed, epithelial-mesenchymal transition (EMT). It is a
conversion of closely connected epithelial cells to highly mobile mesenchymal cells. The
process of EMT is common in embryogenesis, as it is needed for gastrulation and pattern
formation; so, this is another process reactivated in cancer cells. Important characteristics of
EMT include loss of cell polarity, deconstruction of cellular junctions, downregulation of
epithelial markers and the upregulation of mesenchymal markers.
EMT is induced by the tumor-associated stroma which releases factors that stimulate the
transition. Ligand-bound tyrosine kinase receptors on tumor cells activate certain signaling
HC 6
9.1
Organs have well-defined boundaries defined by basement membranes which are acellular
structures made up of extracellular matrix proteins, which keep cells in place. Tumor cells
however compromise this system and are able to metastasize; tumors from a primary site
are able to break free and spread to a distant site. This characteristic feature is only one of
malignant tumors. Metastasis is what makes a cancer lethal, as it interferes with organ
function by physically obstructing or by competing with normal cells for nutrient and
oxygen. It appears though, specific tumors primarily metastasize to certain organs; they
show a preference for an organ, organotropism. This is partially explained by the
directionality of the blood flow, but not always. Cancer cells are like seed and soil; the
metastasizing cells are the seeds, but these require a proper soil to grow. The soil would be
a pre-established niche for the seeds of metastasized tumors to grow. The ability to
metastasize anyway depends on the interactions with cancer cell surface molecules and the
microenvironment (including the ECM). This idea gave rise to the phenomenon of the pre-
metastatic niche. This is a site of future metastasis that is altered to optimally host
metastasized tumor cells in the future. Such an environment is prepared by factors secreted
by the tumor itself, which thus prepare the environment for its arrival.
The metastatic tumor cells from a primary tumor are not clonal, but rather composed of
subpopulations from a genetically identical cells (subclones) differing in mutations due to
evolution. Spreading nevertheless can be monoclonal, seeding by one cell, or polyclonal,
with seeding by multiple subclones. Moreover, the spreading can be linear, one primary
tumor and one metastasis, or branched, with one primary tumor and multiple metastases.
9.2
Metastasis, like carcinogenesis, is a multi-step process on itself. The major steps include
invasion, intravasation, transport, extravasation, and lastly, metastatic colonization.
Additionally, a tumor must not be seen as a clump of proliferating cells, but also the tumor
microenvironment and the tumor-associated stroma is equally important. The metastatic
ability is even determined by the microenvironment.
9.3
The first step of metastasis is invasion. A primary tumor must be able to break free from the
constraints of the local environment and acquire migratory characteristics. This acquisition
or change of the tumor is termed, epithelial-mesenchymal transition (EMT). It is a
conversion of closely connected epithelial cells to highly mobile mesenchymal cells. The
process of EMT is common in embryogenesis, as it is needed for gastrulation and pattern
formation; so, this is another process reactivated in cancer cells. Important characteristics of
EMT include loss of cell polarity, deconstruction of cellular junctions, downregulation of
epithelial markers and the upregulation of mesenchymal markers.
EMT is induced by the tumor-associated stroma which releases factors that stimulate the
transition. Ligand-bound tyrosine kinase receptors on tumor cells activate certain signaling
