Flaxseed has been recognized as a valuable source of nutrients and bioactive compounds, including proteins that possess various health benefits. In recent years, studies have shown that flaxseed proteins, including albumins, globulins, glutelin, and prolamins, possess anti-cancer properties. These properties are attributed to their ability to inhibit cancer cell proliferation, induce apoptosis, and interfere with cancer cell signaling pathways, ultimately leading to the inhibition of metastasis. Moreover, flaxseed proteins have been reported to modulate cancer cell mechanobiology, leading to changes in cell behavior and reduced cancer cell migration and invasion. This review provides an overview of the anti-cancer properties of flaxseed proteins, with a focus on their potential use in cancer treatment. Additionally, it highlights the need for further research to fully establish the potential of flaxseed proteins in cancer therapy.

Metastasis is the main cause of cancer-related mortality; therefore, the ability to predict its propensity can remarkably affect survival rate. Metastasis development is predicted nowadays by lymph-node status, tumor size, histopathology, and genetic testing. However, all these methods may have inaccuracies, and some require weeks to complete. Identifying novel prognostic markers will open an essential source for risk prediction, possibly guiding to elevated patient treatment by personalized strategies. Cancer cell invasion is a critical step in metastasis. The cytoskeletal mechanisms used by metastatic cells for the invasion process are very similar to the utilization of actin cytoskeleton in the endocytosis process. In the current study, the adhesion and encapsulation efficiency of low-cost carboxylate-modified fluorescent nanoparticles by breast cancer cells with high (HM) and low metastatic potential (LM) have been evaluated; benign cells were used as control. Using high-content fluorescence imaging and analysis, we have revealed (within a short time of 1 h), that efficiency of nanoparticles adherence and encapsulation is sufficiently higher in HM cells compared to LM cells, while benign cells are not encapsulating or adhering the particles during experiment time at all. We have utilized custom-made automatic image analysis algorithms to find quantitative co-localization (Pearson’s coefficients) of the nanoparticles with the imaged cells. The method proposed here is straightforward; it does not require especial equipment or expensive materials nor complicated cell manipulations, it may be potentially applicable for various cells, including patient-derived cells. Effortless and quantitative determination of the metastatic likelihood has the potential to be performed using patient-specific biopsy/surgery sample, which will directly influence the choice of protocols for cancer patient’s treatment and, as a result, increase their life expectancy.

Background: The implementation of proton beam irradiation (PBI) for breast cancer (BC) treatment is rapidly advancing due to its enhanced target coverage and reduced toxicities to organs at risk. However, the effects of PBI can vary depending on the cell type. This study aimed to explore the effects of PBI on two BC cell lines, MCF7 and MDA-MB-231. Methods: The relative biological effectiveness (RBE) of PBI was assessed using a clonogenic assay. DNA double-strand break (DSB) repair, epithelial–mesenchymal transition (EMT), and filamentous actin (F-actin) were evaluated using immunofluorescence analysis. The extent of entosis and the senescence-associated β-galactosidase (SA-β-gal) activity were estimated by cytochemistry analysis. The influence of the extracellular matrix was evaluated by cultivating cells in both adherent two-dimensional (2D) environments and within 3D fibrin gels of varying stiffness. The metastatic propensity of cells was investigated using migration tests and the cell encapsulation of carboxylate-modified fluorescent nanoparticles. The comparative tumorigenic potential of cells was investigated using an in vivo model of the chick embryo chorioallantoic membrane (CAM). Results: PBI demonstrated superior efficacy in eliminating MCF7 and MDA-MB-231 cells with RBE 1.7 and 1.75, respectively. Following PBI, MDA-MB-231 cells exhibited significantly lower clonogenic survival compared to MCF7, which was accompanied by the accumulation of phosphorylated histone H2AX (γH2AX), p53-binding protein 1 (53BP1) and Rad51 foci of DNA DSBs repair proteins. After surviving 7 days post-PBI, MCF7 cells exhibited 2.5-fold higher levels of the senescence phenotype and entosis compared to the MDA-MB-231 offspring. Both PBI-survived cell lines had greater capability for 2D collective migration, but their metastatic potential was significantly reduced. A significant influence of extracellular matrix stiffness on the correlation between F-actin expression in PBI-survived cells—an indicator of cell stiffness—and their ability to uptake nanoparticles, a trait associated with metastatic potential, was observed. PBI-survived MDA-MB-231RP subline exhibited a hybrid EMT phenotype and a 70% reduction in tumor growth in the in vivo model of the chick embryo CAM. In contrast, PBI-survived MCF7RP cells exhibit mesenchymal-to-epithelial transition (MET)-like features, and their in vivo tumor growth increased by 66% compared to parental cells. Conclusions: PBI triggers various cellular responses in different BC cell lines, influencing tumor growth through mechanisms like DNA damage repair, stress-induced premature senescence (SIPS), and alterations in the stiffness of tumor cell membranes. Our insights into entosis and the effect of extracellular matrix stiffness on metastatic propensity (nanoparticle uptake) enhance the understanding of the role of PBI in BC cells, emphasizing the need for more research to optimize its therapeutic application.

The major cause (more than 90%) of all cancer-related deaths is metastasis, thus its prediction can critically affect the survival rate. Metastases are currently predicted by lymph-node status, tumor size, histopathology and genetic testing; however, all these are not infallible, and obtaining results may require weeks. The identification of new potential prognostic factors will be an important source of risk information for the practicing oncologist, potentially leading to enhanced patient care through the proactive optimization of treatment strategies. Recently, the new mechanobiology-related techniques, independent of genetics, based on the mechanical invasiveness of cancer cells (microfluidic, gel indentation assays, migration assays etc.), demonstrated a high success rate for the detection of tumor cell metastasis propensity. However, they are still far away from clinical implementation due to complexity. Hence, the exploration of novel markers related to the mechanobiological properties of tumor cells may have a direct impact on the prognosis of metastasis. Our concise review deepens our knowledge of the factors that regulate cancer cell mechanotype and invasion, and incites further studies to develop therapeutics that target multiple mechanisms of invasion for improved clinical benefit. It may open a new clinical dimension that will improve cancer prognosis and increase the effectiveness of tumor therapies.

The main cause of cancer-related mortality is metastasis; thus, its prediction can critically affect the survival rate. Metastases are currently predicted by lymph-node status, tumor size, histopathology and genetic testing, however, all these are not infallible and getting the results may require weeks. The identification new potential prognostic factors will be an important source of risk information for the practicing oncologist, potentially leading to enhanced patient care through the proactive optimization of treatment strategies. We propose to use fluorescent nanoparticles for metastasis detection. Nowadays nanoparticles are widely used for targeted drug delivery, while particles with specific coatings are encapsulated by cancer cells via endocytosis. We have used low-cost carboxylate-modified fluorescent 200 nm particles to achieve the adhesion and encapsulation efficiency of breast cancer cells with high (MDA-MB-231) and low (MCF7) metastatic potential. Using high-content fluorescence imaging microscope (ImageXpress Micro XL), we have discovered that during short time (up to 1h) highly metastatic cells are able to adhere and encapsulate sufficiently more (p<0.05) nanoparticles than lowly metastatic cells. We have created automatic image analysis algorithms to find quantitative colocalization (Pearson’s and Overlap coefficients) of fluorescent nanoparticles with imaged cells. Migration and invasion of cancer cells is a critical step in metastases formation. The cytoskeleton machinery mechanisms (i.e. actin network), utilized by metastatic cells for invasion process have been found similar to the involvement of actin cytoskeleton in endocytosis process. From the other side, for migration process cells use adhesive structures (developed also by nano-particles adhesion) to probe their surroundings and adapt their mechanical properties. We have previously characterized the invasive and migrative abilities of breast cancer cells, as well as patient-derived tumor cells, by indentation and migration assays. We have achieved quantitative and significantly different results for various cancer cells; however, the data-acquisition of such kind assays requires 4-72hs. The obtained results of encapsulation and adhesion efficiency may lead to developing novel clinical tool for metastasis prediction. The proposed here method is very simple, it does not require neither expensive materials and equipment nor cell manipulations (e.g. serum starvation, staining, expansion), it is potentially suitable for a variety of cells. Rapid (up to 1h), quantitative, patient-specific determination of the metastatic likelihood from biopsy/surgery sample, will directly affect the choice of treatment protocols for cancer patients and eventually increase their life-expectancy. Citation Format: Yulia Merkher, Elizaveta Kontareva, Anna Melekhova, Sergey Leonov. Nanoparticles imaging for cancer metastasis diagnosis [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-042.

Flaxseed has been recognized as a valuable source of nutrients and bioactive compounds, including proteins that possess various health benefits. In recent years, studies have shown that flaxseed proteins, including albumins, globulins, glutelin, and prolamins, possess anti-cancer properties. These properties are attributed to their ability to inhibit cancer cell proliferation, induce apoptosis, and interfere with cancer cell signaling pathways, ultimately leading to the inhibition of metastasis. Moreover, flaxseed proteins have been reported to modulate cancer cell mechanobiology, leading to changes in cell behavior and reduced cancer cell migration and invasion. This review provides an overview of the anti-cancer properties of flaxseed proteins, with a focus on their potential use in cancer treatment. Additionally, it highlights the need for further research to fully establish the potential of flaxseed proteins in cancer therapy.