Page 27 - TD-3-2

Tumor Discovery Vasculoendothelium, bone, and cancer in obese children

growth factors and chemokines release, and interacting and pathological condition may lead to new therapeutic
with different cell types. Endothelial cells in bone have approaches for a range of bone conditions.
several functions, namely maintenance of vascular
integrity, bone formation, and direct stimulation of 2.3.1. VED and its implications in cancer
osteoblasts/osteoclasts crosstalk. 6 VED is characterized by an imbalance in the production

Alterations of the complex biochemical interactions and release of various substances by endothelial cells,
between vasculature and bone cells dramatically affect leading to altered vascular tone, increased inflammation,
bone metabolism and health and may lead to various and impaired blood vessel function. While VED is
clinical manifestations. Changes to the blood supply in commonly associated with cardiovascular diseases,
the vascular networks surrounding bone cells very often emerging research has also highlighted its implications
could lead to inhibition of bone metabolism, resulting in for cancer development and progression. VED can
decreased bone formation. contribute to increased angiogenesis, which is a critical
process for supplying tumors with nutrients and
Obesity influences bone metabolism by stimulating oxygen in cancer patients, facilitating their growth and
pre-osteoblasts to differentiate into adipocytes rather than progression. Endothelial dysfunction is often associated
osteoblasts, thus filling the cavities of bone marrow with with chronic inflammation. Inflammation in the tumor
adipocytes rather than trabecular bone, consequently microenvironment can promote cancer development and
increasing bone fragility. The RANKL/RANK/OPG contribute to the evasion of immune surveillance. The
pathway is a signaling pathway that regulates the formation dysfunctional endothelium may facilitate the recruitment
and activity of osteoclasts, which are cells responsible of immune cells that support tumor growth. Dysfunction
for breaking down bone tissue. Increased levels of pro- of the vascular endothelium can lead to increased
inflammatory cytokines due to obesity would dysregulate permeability of blood vessels that might contribute to the
this pathway, leading to an increase in osteoclast formation intravasation and extravasation of cancer cells, facilitating
and activity. Ultimately, this results in a decrease in bone their spread to distant sites and promoting metastasis.
density and an increased risk of fractures. Therefore, it
is crucial to maintain a healthy weight through proper Endothelial dysfunction can induce a procoagulant
dietary intake and exercise, especially for obese children, state and may contribute to cancer-associated thrombosis,
to ensure good bone health. 7 a common complication in cancer patients. Cancer cells
can influence the endothelium through the release of
Obesity is related to inflammatory musculoskeletal various factors that may further exacerbate VED and create
diseases (i.e., osteoarthritis). VED in obese children a microenvironment conducive to tumor growth.
8
manifests in several ways, impacting various aspects of
musculoskeletal function. Endothelial NO bioavailability Markers of VED, such as elevated levels of circulating
is significantly reduced in obesity, leading to impaired endothelial cells, von Willebrand factor (vWF), and
vasodilation and decreased blood flow to muscles and adhesion molecules, have been investigated for their
causing diminished exercise capacity, muscle fatigue, and diagnostic and prognostic value in cancer. These markers
reduced exercise tolerance, which poses a hindrance to may serve as indicators of the vascular changes associated
physical activity participation, thereby perpetuating the with tumor development.
obesity cycle. Furthermore, VED promotes chronic low- Targeting VED has become an area of interest in cancer
grade inflammation, contributing to muscle weakness, pain, therapeutics. Anti-angiogenic therapies are conceptualized
and impaired bone health, all of which increase the risk of to disrupt the formation of new blood vessels so as to impede
musculoskeletal injuries and fractures. VED also promotes tumor growth. In addition, drugs targeting inflammation and
pro-thrombotic changes, increasing the risk of deep vein endothelial function are being explored in cancer treatment.
thrombosis and other musculoskeletal complications. 9 Understanding the intricate relationship between VED
Spatiotemporal interaction between endothelial and cancer is essential for developing targeted therapeutic
cells and neighboring skeletal cells plays critical roles strategies and improving patient outcomes. The molecular
in development, homeostasis, and pathological bone and cellular mechanisms underlying this relationship are
destruction. The altered relationship between endothelium, currently under exploration in ongoing research.
vasculature, and bone tissue can result in pathologies such
as avascular necrosis, osteopetrosis, rickets, osteoporosis, 2.3.2. Vascular endothelium and bone sarcomas
inflammatory bone loss, multiple myeloma, Paget’s disease, In the context of bone sarcoma, the interaction between
and metastatic bone disease. Thus, a greater understanding cancer cells and the vascular endothelium in the bone
of the role of bone vasculature in both normal development microenvironment plays a critical role. Osteosarcoma is the
10

Volume 3 Issue 2 (2024) 3 doi: 10.36922/td.2825