Abstract
The spreading of cancer cells, also known as metastasis, is a lethal hallmark in cancer progression and the primary cause of cancer death. Recent cancer research has suggested that the remodeling of collagen fibers in the extracellular matrix (ECM) of the tumor microenvironment facilitates the migration of cancer cells during metastasis. ECM remodeling refers to the following two procedures: the ECM degradation caused by enzyme matrix metalloproteinases and the ECM alignment due to the cross-linking enzyme lysyl oxidase (LOX). Such modifications of ECM collagen fibers result in changes of ECM physical and biomechanical properties that affect cancer cell migration through the ECM. However, the mechanism of such cancer migration through a remodeling ECM remains not well understood. A mathematical model is proposed in this work to better describe and understand cancer migration by means of ECM remodeling. Effects of LOX are considered to enable transport of enzymes and migration of cells through a dynamic, reactive tumor microenvironment that is modulated during cell migration. For validation cases, the results obtained show comparable trends to previously established models. In novel test cases, the model predicts the impact on ECM remodeling and the overall migration of cancer cells due to the inclusion of LOX, which has not yet been included in previous cancer invasion models.
Highlights
Every year there are approximately 8.2 million cancer-related deaths worldwide
Metastasis is a systematic process that involves the interaction of cancer cells among a community of various biochemical and cellular factors localized in the tumor microenvironment at both the primary and secondary tumor sites [1]
Results of Case III have confirmed the capability of our new model to successfully implement the extended features to capture the cross-linking effect that lysyl oxidase (LOX) performs on the extracellular matrix (ECM)
Summary
Every year there are approximately 8.2 million cancer-related deaths worldwide. Metastasis is the primary cause of cancer death. Many recent cancer-related studies have pointed out that the primary tumor microenvironment contains many important factors that determine whether the primary tumor progresses and proceeds to metastasize or remains dormant, staying a benign tumor [2,3,4,5,6]. In the early stage of metastatic cancer invasion, migration of cancer cells first takes place by breaking away from the primary tumor site and breaching the basement membrane of the tumor. This thin barrier underlying the tumor mass is made up of mostly type IV collagen fibers that separate the tumor from the extracellular matrix (ECM) [7].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
