Biology subjects

Pesen-Okvur, D.

Publications and source records attributed to Pesen-Okvur, D..

4 recordsLinked to original sources

bioRxiv2026

Magnetic Levitation of Intact Tumor Biopsies Reveals Multivariate Biophysical Signatures of Breast Cancer Aggressiveness

Diagnostic assessment of breast cancer biopsies remains reliant on resource-intensive histopathology and molecular profiling, which often lack real-time physiological readouts. Magnetic levitation (MagLev) enables label-free density profiling of single cells, yet its application to intact tissue biopsies has been precluded by size-dependent geometric artifacts and the absence of analytical frameworks for biopsy-scale samples. Here, we report the first application of MagLev to intact invasive breast carcinoma biopsies (200-600 m) for biophysical profiling, generating multivariate biophysical signatures from 203 samples across 17 patients. We developed a physics-based size-correction algorithm (xmc) that isolates biological density from geometric artifact, and demonstrate that tissue viability is predicted not by average levitation height, but by spatial heterogeneity across replicate samples, reflecting the microenvironmental complexity of metabolically active tumors. Multivariate integration using Partial Least Squares (PLS) regression and Factor Analysis of Mixed Data (FAMD) identified nodal status (N) as the strongest biophysical predictor, suggesting that lymphatic dissemination capacity leaves a measurable signature in the primary tumor density profile. Unsupervised patient clustering in PLS-derived latent space recovered three clinically coherent subgroups aligned with molecular subtypes. This 30-minute, low-cost assay provides exploratory biophysical stratification complementary to existing diagnostics, particularly in resource-limited settings.

bioengineering↗

bioRxiv2024

Cancer cell-derived extracellular matrix promotes differentiation of fibroblasts into cancer-associated fibroblasts

Breast cancer is the most common cancer and the leading cause of cancer-related mortality in women. In addition to cancer cells, the bulk of a breast tumor comprises a range of stromal cell types, including fibroblasts. Cancer-associated fibroblasts (CAF) are crucial players in the tumor microenvironment; however, the process by which fibroblasts differentiate into CAFs is not fully understood. Extracellular matrix (ECM) is known to modulate cell phenotypes. Decellularized ECM (dECM) is a useful tool for studying in-vitro cell-ECM interactions. Yet, whether cancer cell-derived ECM (ccECM) has a role in CAF formation is not known. Here, we optimized the culture duration (5 days) and the extraction method (freeze-thaw) for obtaining ccECM. We confirmed the presence of ccECM using coomassie blue staining and scanning electron microscopy. We showed that ccECM contained fibronectin and laminin using immunofluorescence staining. In addition, we showed that the presence of ccECM but not glass surface or TGF{beta} promoted the initial adhesion of fibroblasts, as expected. Finally, using quantitative immunofluorescence microscopy, we demonstrated that in contrast to fibroblasts cultured on glass surfaces in the presence and absence of TGF{beta}, fibroblasts cultured on ccECM showed increased expression of CAF markers vimentin (2.8 fold), FAP (3.4 fold) and PDGFR {beta} (1.8 fold), but not FSP1/s100A4. Overall, our results indicate that ccECM promotes the differentiation of fibroblasts into CAFs.

cancer biology↗

bioRxiv2020

Homing Choices of Breast Cancer Cells Revealed by Tissue Specific Invasion and Extravasation Lab-on-a-chip Platforms

Metastasis is one of the major obstacles for breast cancer patients. Limitations of current models demand the development of novel platforms to predict metastatic potential and homing choices of cancer cells. Here, two novel Lab-on-a-chip (LOC) platforms, invasion/chemotaxis (IC-chip) and extravasation (EX-chip), are presented for the quantitative assessment of invasion and extravasation, towards specific tissues. On IC-chip, invasive MDA-MB-231, but not non-invasive MCF-7 breast cancer cells invaded lung and liver microenvironments. Lung-specific but not bone-specific MDA-MB-231 clones efficiently invaded lung microenvironment, stressing ability of IC-chip to demonstrate different in vivo metastatic behaviors. On EX-chip, MDA-MB-231 cells extravasated more into the lung microenvironment compared to the liver and breast highlighting the potency of the platform to mimic in vivo homing choices. Overall, this study presents IC-chip and EX-chip that can determine tissue-specific invasion and extravasation potentials of cancer cells providing the groundwork for novel diagnostic tools to predict metastasis risk.

cancer biology↗

bioRxiv2020

Breast Cancer Cells and Macrophages in a Paracrine-Juxtacrine Loop

Breast cancer cells (BCC) and macrophages are known to interact via epidermal growth factor (EGF) produced by macrophages and colony stimulating factor-1 (CSF-1) produced by BCC. Despite contradictory findings, this interaction is perceived as a paracrine loop. Further, the underlying mechanism of interaction remains unclear. Here, we investigated interactions of BCC with macrophages in 2D and 3D. BCC did not show chemotaxis to macrophages in custom designed 3D cell-on-a-chip devices, which was in agreement with ELISA results showing that macrophage-derived-EGF was not secreted into macrophage-conditioned-medium. Live cell imaging of BCC in the presence and absence of iressa showed that macrophages but not macrophage-derived-matrix modulated adhesion and motility of BCC in 2D. 3D co-culture experiments in collagen and matrigel showed that BCC changed their multicellular organization in the presence of macrophages. In custom designed 3D co-culture cell-on-a-chip devices, macrophages promoted and reduced migration of BCC in collagen and matrigel, respectively. Furthermore, adherent but not suspended BCC endocytosed EGFR when in contact with macrophages. Collectively, our data revealed that macrophages showed chemotaxis towards BCC whereas BCC required direct contact to interact with macrophage-derived-EGF. We propose that the interaction between cancer cells and macrophages is a paracrine-juxtacrine loop of CSF-1 and EGF, respectively.

cancer biology↗