Historically, cancer has been described as originating from modified cells, because of mutations impacting their growth, their differentiation and their way (not) to die. Now, it is widely acknowledged that the microenvironment surrounding these cells is involved in cancer initiation and progression.
As explained in the article by Nia Munn & Jain published in Science, the proliferation of cancer cells is linked to a disruption of surrounding structures – including the extracellular matrix (ECM) – through physical and biochemical mechanisms (Figure below).
First, solid stresses are the mechanical forces linked to solid and elastic elements of the ECM and cells. These stresses can be of compressive, tensile and shear nature. Multiple mechanisms are involved, like increased tissue volume, displacement of neighbouring normal tissue, swelling of ECM elements like Hyaluronic acid, etc.
Second, interstitial fluid pressure is another important physical parameter in tumors. Indeed, many cancers exhibit disturbed fluid drainage because of hyperpermeable blood and lymphatic vessels compressed by the solid stress.
Third, an increased tissue stiffness (or rigidity) is at stake in tumoral state. Defined as the resistance of a material to deformation in response to a force, the stiffness is an intrinsic property of materials – and of cancer tissues, importantly. In many different solid cancers (breast, pancreatic, liver, brain, prostate…), the malignant tumor is much stiffer than the benign tumor. For this reason, this parameter has been used as a diagnostic, and more recently, prognostic factor.
Last but not least, the microarchitecture of the ECM and microanatomy of cells and tissues should also be taken into account. These are different from one (healthy) cell and one tissue from another, and are modified in cancerous transformation. As an illustration, breast cancer cells have very different behaviours, morphologies when cultured in 2D layers vs in 3D !
As a conclusion, the tumor microenvironmenet is modified both at the biological and physical levels. There is growing interest in studying physical parameters in cancer initiation and progression, in order to better counteract cancer development in patients and find efficient anti-cancer therapies – targeting not only cancer cells but also their surroundings.
In HCS Pharma, we are convinced that the physical features of cancer tissues should be looked carefully in preclinical in vitro studies. In this frame, we are working on BIOMIMESYS® 3D cell culture system, as a relevant ECM surrogate, to propose a range of products with different stiffnesses that fit the different physical realities of cancers. Stay tuned!