Tumor‐Associated Protrusion Fluctuations as a Signature of Cancer Invasiveness

Abstract

The generation of invasive fluctuating protrusions is a distinctive feature of tumor dissemination. During the invasion, individual cancer cells modulate the morphodynamics of protrusions to optimize their migration efficiency. However, it remains unclear how protrusion fluctuations govern the invasion of more complex multi‐cellular structures, such as tumors, and their correlation with the tumor metastatic potential. Herein, a reductionist approach based on 3D tumor cell micro‐spheroids with different invasion capabilities is used as a model to decipher the role of tumor‐associated fluctuating protrusions in cancer progression. To quantify fluctuations, a set of key biophysical parameters that precisely correlate with the invasive potential of tumors is defined. It is shown that different pharmacological drugs and cytokines are capable of modulating protrusion activity, significantly altering protrusion fluctuations, and tumor invasiveness. This correlation is used to define a novel quantitative invasion index encoding the key biophysical parameters of fluctuations and the relative levels of cell‐cell/matrix interactions, which is capable of assessing the tumor's metastatic capability solely based on its magnitude. Overall, this study provides new insights into how protrusion fluctuations regulate tumor cell invasion, suggesting that they may be employed as a novel early indicator, or biophysical signature, of the metastatic potential of tumors.

Viscoelastic Liquid Matrix with Faster Bulk Relaxation Time Reinforces the Cell Cycle Arrest Induction of the Breast Cancer Cells via Oxidative Stress

“…After 1 d of culture, the thickness of the substrates decreased to ~15 μm ( Figure S4 ). Despite the decrease in substrate thickness over 5 d of cell culturing, the substrate thickness remained in the acceptable range for avoiding the cell sensing of the underneath coverslip glass; because the MCF7 cell protrusion length was ~7 μm [ 36 ]. The interface of the substrates was relatively flat.…”

Shining a Light on Cancer—Photonics in Microfluidic Tumor Modeling and Biosensing

“…[108] This work paves the way for optofluidic-driven analysis of micromechanical events, highly relevant in living tissues and cancer, [14] where fluctuations of cancer-associated protrusions represent a clear signature of cancer invasiveness. [109] These results show how the combination of live cell imaging in microfluidic settings can take advantage of optofluidic strategies for real-time detection of cellular shape, composition, and mechanics, where a wide range of cancer cell responses and premetastatic events can be monitored with unprecedented efficacy. The tracking of those signatures can be further combined with studies on drugs of interest, boosting the discovery of effectiveness in much more complex and in vivo-like responses.…”

Red blood cell-tumour cell interactions promote tumour cell progression

“…We could observe that cancer cells in the presence of RBCs, especially from metastatic cancer patients, change cell morphology, transitioning from a rounded shape to a more mesenchymal cell type with lamellipodia-like protrusions, key membrane structures involved in chemo-sensing and migration [31][32][33] and commonly associated with increased metastatic potential 34 . Furthermore, we also observed that tumour cell lines show enhanced migratory and adhesive capabilities after having direct contact with RBCs from cancer patients.…”