Cellular Mechanisms of Circulating Tumor Cells During Breast Cancer Metastasis

Abstract

Circulating tumor cells (CTCs) are cancer cells that detach from the primary site and travel in the blood stream. A higher number of CTCs increases the risk of breast cancer metastasis, and it is inversely associated with the survival rates of patients with breast cancer. Although the numbers of CTCs are generally low and the majority of CTCs die in circulation, the survival of a few CTCs can seed the development of a tumor at a secondary location. An increasing number of studies demonstrate that CTCs undergo modification in response to the dynamic biophysical environment in the blood due in part to fluid shear stress. Fluid shear stress generates reactive oxygen species (ROS), triggers redox-sensitive cell signaling, and alters the function of intracellular organelles. In particular, the mitochondrion is an important target organelle in determining the metastatic phenotype of CTCs. In healthy cells, mitochondria produce adenosine triphosphate (ATP) via oxidative phosphorylation in the electron transport chain, and during oxidative phosphorylation, they produce physiological levels of ROS. Mitochondria also govern death mechanisms such as apoptosis and mitochondrial permeability transition pore opening to, in order eliminate unwanted or damaged cells. However, in cancer cells, mitochondria are dysregulated, causing aberrant energy metabolism, redox homeostasis, and cell death pathways that may favor cancer invasiveness. In this review, we discuss the influence of fluid shear stress on CTCs with an emphasis on breast cancer pathology, then discuss alterations of cellular mechanisms that may increase the metastatic potentials of CTCs.

Morphological Phenotyping of Organotropic Brain- and Bone-Seeking Triple Negative Metastatic Breast Tumor Cells

“…Breast tumor cells circulate in a suspended state in the blood stream during the metastatic cascade, prior to adhesion to the vascular endothelium ( Mentis et al, 2020 ). Circulating tumor cells are associated with increased risk of metastasis and lower progression-free and overall survival in breast cancer patients ( Bidard et al, 2014 ; Riebensahm et al, 2019 ; Cristofanilli et al, 2019 ; Park et al, 2020 ). We first questioned whether the three breast tumor cell clones had different sizes in suspension.…”

Combining nanotechnology with the multifunctional roles of neutrophils against cancer and inflammatory disease

“…CTCs play an important role in tumor progression because of their great metastasis potential, and can circulate and disseminate within the body to seed and colonize metastasis niches. 53 For this reason, CTCs are considered as therapeutic targets for metastasis inhibition. Accumulating pieces of evidence have shown that inflammatory neutrophils are capable of targeting CTCs both in circulation and in metastasis niches due to the vascular cell adhesion molecule-1 (VCAM-1) expressed on the neutrophil membrane.…”

Emerging nanomedicine-based therapeutics for hematogenous metastatic cascade inhibition: Interfering with the crosstalk between “seed and soil”

“…Besides, though CTCs are identified to express both EMT and CSCs markers 115 , they may obtain extra molecular changes during EMT and circulation. Specifically, multiple cellular mechanisms are activated and CTCs are modified to be heterogeneous with enhanced metastatic potential, bringing extra challenges for targeted drug delivery 116 , 117 . Fortunately, various novel targeting tools as well as nanovehicles have been introduced to broaden the arsenal fighting against CTCs by virtue of advanced molecular and biomedical engineering technology.…”