Minwoo Kang

All Publications

• Classification of differentially activated groups of fibroblasts using morphodynamic and motile features APL BIOENGINEERING Kang, M., Min, C., Devarasou, S., Shin, J. H. 2025; 9 (2): 026116

  Abstract

  Fibroblasts play essential roles in cancer progression, exhibiting activation states that can either promote or inhibit tumor growth. Understanding these differential activation states is critical for targeting the tumor microenvironment (TME) in cancer therapy. However, traditional molecular markers used to identify cancer-associated fibroblasts are limited by their co-expression across multiple fibroblast subtypes, making it difficult to distinguish specific activation states. Morphological and motility characteristics of fibroblasts reflect their underlying gene expression patterns and activation states, making these features valuable descriptors of fibroblast behavior. This study proposes an artificial intelligence-based classification framework to identify and characterize differentially activated fibroblasts by analyzing their morphodynamic and motile features. We extract these features from label-free live-cell imaging data of fibroblasts co-cultured with breast cancer cell lines using deep learning and machine learning algorithms. Our findings show that morphodynamic and motile features offer robust insights into fibroblast activation states, complementing molecular markers and overcoming their limitations. This biophysical state-based cellular classification framework provides a novel, comprehensive approach for characterizing fibroblast activation, with significant potential for advancing our understanding of the TME and informing targeted cancer therapies.

  View details for DOI 10.1063/5.0250502

  View details for Web of Science ID 001490597900001

  View details for PubMedID 40385989

  View details for PubMedCentralID PMC12084086

• EMT induction in normal breast epithelial cells by <i>COX2</i>-expressing fibroblasts CELL COMMUNICATION AND SIGNALING Kang, M., Devarasou, S., Sung, N., Kwon, T., Shin, J. H. 2025; 23 (1): 237

  Abstract

  The tumor microenvironment (TME) plays a pivotal role in cancer progression, with cancer-associated fibroblasts (CAFs) significantly influencing tumor behavior. Especially, elevated COX2 expressing fibroblasts within the TME, notably in collagen-dense tumors like breast cancer, has been recently emphasized in the literature. However, the specific effect of COX2-expressing CAFs (COX2+ CAFs) on neighboring cells and their consequent role in cancer progression is not fully elucidated.We induced COX2+ fibroblasts by forcing the fibroblasts forming aggregates to undergo Nemosis as a proxy for COX2+ CAFs. This approach enabled us to simulate the paracrine interactions between COX2+ CAFs and normal breast epithelial cells via conditioned media from COX2+ fibroblasts. We developed an innovative in vitro platform that combines cell mechanics-based analysis and biomolecular assays to study the interactions between COX2+ fibroblasts and normal breast epithelial cells. By focusing on the mechanical characteristics of the cells and the epithelial-mesenchymal transition (EMT) marker expressions, we aimed to elucidate the paracrine mechanisms through which COX2+ CAFs influence the tumor microenvironment.Our in vitro findings demonstrate that COX2+ fibroblasts, through conditioned media, induce significant alterations in the mechanical behavior of normal breast epithelial cells, as evidenced by monolayer expansion measurements using traction force microscopy (TFM). This transition was further corroborated by single-cell morphology and motility analyses, as well as increased expression of mesenchymal markers, including SNAI1 at the mRNA level and vimentin at the protein level. EP4 inhibition partially reversed these changes, preserving cell-cell interactions, limiting monolayer expansion, and reducing mesenchymal-like features, suggesting that PGE2-EP4 signaling plays a key role in mediating the paracrine effects of COX2+ fibroblasts. Together, our findings support a model in which PGE2-EP4 signaling contributes to EMT induction, potentially involving SNAI1 regulation, with implications for targeting stromal-epithelial interactions in breast cancer.This study advances our understanding of the potential mechanisms by which COX2+ CAFs influence tumor progression within the breast tumor microenvironment (TME) through controlled in vitro investigations. By integrating cell mechanics-based analysis, biomolecular assays, and innovative in vitro cell-based modeling of COX2+ CAFs, we have delineated the contributory role of these cells in a controlled setting. These insights lay a groundwork for future studies that could explore the implications of these findings in vivo, potentially guiding targeted therapeutic strategies.

  View details for DOI 10.1186/s12964-025-02227-7

  View details for Web of Science ID 001493136500001

  View details for PubMedID 40405218

  View details for PubMedCentralID PMC12100922

• Tension-sensitive HOX gene expression in fibroblasts for differential scar formation JOURNAL OF TRANSLATIONAL MEDICINE Kang, M., Ko, U., Oh, E., Kim, H., Chung, H., Shin, J. H. 2025; 23 (1): 168

  Abstract

  Scar formation is a common end-point of the wound healing process, but its mechanisms, particularly in relation to abnormal scars such as hypertrophic scars and keloids, remain not fully understood. This study unveils a novel mechanistic insight into scar formation by examining the differential expression of Homeobox (HOX) genes in response to mechanical forces in fibroblasts derived from normal skin, hypertrophic scars, and keloids.We isolated fibroblasts from different scar types and conducted RNA sequencing (RNA-Seq) to identify differential gene expression patterns among the fibroblasts. Computational modeling provided insight into tension alterations following injury, and these findings were complemented by in vitro experiments where fibroblasts were subjected to exogenous tensile stress to investigate the link between mechanical tension and cellular behavior.Our study revealed differential HOX gene expression among fibroblasts derived from normal skin, hypertrophic scars, and keloids. Computational simulations predicted injury-induced tension reduction in the skin, and in vitro experiments revealed a negative correlation between tension and fibroblast proliferation. Importantly, we discovered that applying mechanical tension to fibroblasts can modulate HOX gene expression, suggesting a pivotal role of mechanical cues in scar formation and wound healing.This study proposes a model wherein successful wound healing and scar formation are critically dependent on maintaining tensional homeostasis in the skin, mediated by tension-sensitive HOX genes. Our findings highlight the potential of targeting mechanotransduction pathways and tension-sensitive HOX gene expression as therapeutic strategies for abnormal scar prevention and treatment, offering a new perspective on the complex process of scar formation.

  View details for DOI 10.1186/s12967-025-06191-1

  View details for Web of Science ID 001418730000005

  View details for PubMedID 39930512

  View details for PubMedCentralID PMC11808978

• Biophysical perspectives to understanding cancer-associated fibroblasts APL BIOENGINEERING Devarasou, S., Kang, M., Shin, J. H. 2024; 8 (2): 021507

  Abstract

  The understanding of cancer has evolved significantly, with the tumor microenvironment (TME) now recognized as a critical factor influencing the onset and progression of the disease. This broader perspective challenges the traditional view that cancer is primarily caused by mutations, instead emphasizing the dynamic interaction between different cell types and physicochemical factors within the TME. Among these factors, cancer-associated fibroblasts (CAFs) command attention for their profound influence on tumor behavior and patient prognoses. Despite their recognized importance, the biophysical and mechanical interactions of CAFs within the TME remain elusive. This review examines the distinctive physical characteristics of CAFs, their morphological attributes, and mechanical interactions within the TME. We discuss the impact of mechanotransduction on CAF function and highlight how these cells communicate mechanically with neighboring cancer cells, thereby shaping the path of tumor development and progression. By concentrating on the biomechanical regulation of CAFs, this review aims to deepen our understanding of their role in the TME and to illuminate new biomechanical-based therapeutic strategies.

  View details for DOI 10.1063/5.0199024

  View details for Web of Science ID 001240225300001

  View details for PubMedID 38855445

  View details for PubMedCentralID PMC11161195

• Influence of Transforming Growth Factors beta 1 and beta 3 in the Scar Formation Process JOURNAL OF CRANIOFACIAL SURGERY Lee, J., Cho, H., Lee, J., Oh, E., Kim, H., Ko, U., Kang, M., Shin, J. H., Chung, H. 2023; 34 (3): 904-909

  View details for DOI 10.1097/SCS.0000000000009087

  View details for Web of Science ID 001012652600063

• Fibrous Matrix Architecture-Dependent Activation of Fibroblasts with a Cancer-Associated Fibroblast-like Phenotype ACS BIOMATERIALS SCIENCE & ENGINEERING Devarasou, S., Kang, M., Kwon, T., Cho, Y., Shin, J. H. 2023; 9 (1): 280-291

  Abstract

  Cancer-associated fibroblasts (CAFs) are one of the most prevalent cell types within the tumor microenvironment (TME). While several physicochemical cues from the TME, including growth factors, cytokines, and ECM specificity, have been identified as essential factors for CAF activation, the precise mechanism of how the ECM architecture regulates CAF initiation remains elusive. Using a gelatin-based electrospun fiber mesh, we examined the effect of matrix fiber density on CAF activation induced by MCF-7 conditioned media (CM). A less dense (3D) gelatin mesh matrix facilitated better activation of dermal fibroblasts into a CAF-like phenotype in the CM than a highly dense (3D) gelatin mesh matrix. In addition, it was discovered that CAF activation on the less dense (LD) matrix is dependent on the cell size-related AKT/mTOR signaling cascade, accompanied by an increase in intracellular tension within the well-spread fibroblasts.

  View details for DOI 10.1021/acsbiomaterials.2c00694

  View details for Web of Science ID 000906132200001

  View details for PubMedID 36573928

• Numerical study on sediment erosion of Francis turbine with different operating conditions and sediment inflow rates Kang, M., Park, N., Suh, S. edited by Taler, J., Mohamad, A., Benim, A. C. ELSEVIER SCIENCE BV. 2016: 457-464

  View details for DOI 10.1016/j.proeng.2016.08.389

  View details for Web of Science ID 000383947400059