Male Fisher 344 rats were purchased in Japan SLC (Shizuoka, Japan). The rat aorta smooth muscle cell line, A7r5, was acquired from DS Pharma Biomedical Co. Limited (Osaka, Japan). A persons cervical cancer cell line, HeLa, and also the human osteosarcoma cell line, HOS, were acquired in the Health Science Research Sources Bank (Osaka, Japan). Cell culture medium was purchased in Sigma-Aldrich (St. Louis, MO). Fetal bovine serum (FBS) was purchased in JRH Biosciences (Lenexa, KS). Antibiotics were purchased in Existence Technologies Japan Limited. (Tokyo, japan, Japan). Other reagents were purchased in Wako Pure Chemical Industries Limited. (Osaka, Japan), Sigma-Aldrich, and Existence Technologies Japan Limited.
Cellular automata (CA) are pretty straight forward mixers can simulate complex processes both in space and time. A CA includes six defining components: a framework, cells, an area, rules, initial conditions, as well as an update sequence. CA models are pretty straight forward, nominally deterministic yet able to showing phase changes and emergence, map easily to the data structures utilized in geographic computer, and are simple to implement and understand. It has led to their recognition for applications for example calculating land use changes and monitoring disease spread, among many more.
Understanding tumor invasion and metastasis is of crucial importance for both fundamental cancer research and clinical practice. In vitro experiments have established that the invasive growth of malignant tumors is characterized by the dendritic invasive branches composed of chains of tumor cells emanating from the primary tumor mass. The preponderance of previous tumor simulations focused on non-invasive (or proliferative) growth. The formation of the invasive cell chains and their interactions with the primary tumor mass and host microenvironment are not well understood. Here, we present a novel cellular automaton (CA) model that enables one to efficiently simulate invasive tumor growth in a heterogeneous host microenvironment. By taking into account a variety of microscopic-scale tumor-host interactions, including the short-range mechanical interactions between tumor cells and tumor stroma, degradation of the extracellular matrix by the invasive cells and oxygen/nutrient gradient driven cell motions, our CA model predicts a rich spectrum of growth dynamics and emergent behaviors of invasive tumors. Besides robustly reproducing the salient features of dendritic invasive growth, such as least-resistance paths of cells and intrabranch homotype attraction, we also predict nontrivial coupling between the growth dynamics of the primary tumor mass and the invasive cells. In addition, we show that the properties of the host microenvironment can significantly affect tumor morphology and growth dynamics, emphasizing the importance of understanding the tumor-host interaction. The capability of our CA model suggests that sophisticated in silico tools could eventually be utilized in clinical situations to predict neoplastic progression and propose individualized optimal treatment strategies.