Tumor-associated Endo180 requires stromal-derived LOX to promote metastatic prostate cancer cell migration on human ECM surfaces

Caley, Matthew; King, H. W.; Shah, Neel; Wang, Kai; Rodriguez-Teja, Mercedes; Gronau, Julian Hendrik; Waxman, Jonathan; Sturge, Justin

doi:10.1007/s10585-015-9765-7

Cited by 19 publications

(23 citation statements)

References 61 publications

(88 reference statements)

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“…44,45 Stromal-derived LOX could create a milieu that is suitable for metastastic cancer cells. 34,46 Recently, LOX has been considered as one target to control the metastasis of prostate cancer. 46,47 MMPs may be the target for LOX in the process of ECM remodeling.…”

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confidence: 99%

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Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

Peng

Liu

Yang

et al. 2017

IJN

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Purpose Semiconductor quantum dots (QDs) are a promising alternative to organic fluorescent dyes for multiplexed molecular imaging of cancer stroma, which have great advantages in holistically analyzing the complex interactions among cancer stromal components in situ. Patients and methods A QD probe-based multiplexed spectral molecular imaging method was established for simultaneous imaging. Three tissue microarrays (TMAs) including 184 gastric cancer (GC) tissues were constructed for the study. Multispectral analyses were performed for quantifying stromal biomarkers, such as lysyl oxidase (LOX). The stromal status including infiltrating of immune cells (high density of macrophages), angiogenesis (high density of microvessel density [MVD], low neovessel maturation) and extracellular matrix (ECM) remodeling (low density of type IV collagen, intense expression of matrix metalloproteinase 9 [MMP-9]) was evaluated. Results This study compared the imaging features of the QD probe-based single molecular imaging method, immunohistochemistry, and organic dye-based immunofluorescent methods, and showed the advantages of the QD probe-based multiple molecular imaging method for simultaneously visualizing complex components of cancer stroma. The risk of macrophages in high density, high MVD, low neomicrovessel maturation, MMP-9 expression and low type IV collagen was significantly increased for the expression of LOX. With the advantages of the established QD probe-based multiplexed molecular imaging method, the spatial relationship between LOX and stromal essential events could be simultaneously evaluated histologically. Stromal activation was defined and then evaluated. Survival analysis showed that the stromal activation was correlated with overall survival and disease-free survival ( P <0.001 for all). The expression of LOX was significantly increased in the intense activation subgroup ( P <0.001). Conclusion Quantifying assessment of the stroma indicates that the LOX may be a stromal marker for GC and stromal activation, which is not only responsible for the ECM remodeling morphologically, but also for the formation of invasive properties and recurrence. These results support the possibility to integrate morphological and molecular biomarker information for cancer research by the biomedical application of QDs.

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confidence: 99%

“…34,46 Recently, LOX has been considered as one target to control the metastasis of prostate cancer. 46,47 MMPs may be the target for LOX in the process of ECM remodeling. 38,48 It is noteworthy that LOX mediates cell migration provoked by LKB1 loss with little impact on cell proliferation in 2D cell culture.…”

mentioning

confidence: 99%

Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

Peng

Liu

Yang

et al. 2017

IJN

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“…10. To study the effect of stiff (AGE-rich) rBM on prostate tumor cell migration, image PC3 cells using brightfield video time-lapse microscopy using temperature/CO 2 control and a humidified chamber 17 . Note: PC3 cells grow in strands on native rBM and do not form acini with a lumen, but if left to grow more than 72 hr on native rBM they will form 3D spheroids .…”

Section: D Culture Of Prostate Tumor Cell Aggregates On Native and Smentioning

confidence: 99%

“…11. Following data acquisition, manually track PC3 cells and calculate their migration speed, shape (elongation ratio) and persistence of migration [17][18][19] . Note: Persistence = ratio D/T, D = distance from start to end of cell trajectory, T = total length of cell trajectory.…”

Section: D Culture Of Prostate Tumor Cell Aggregates On Native and Smentioning

confidence: 99%

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How to Study Basement Membrane Stiffness as a Biophysical Trigger in Prostate Cancer and Other Age-related Pathologies or Metabolic Diseases

Rodriguez-Teja

Breit

Clarke

et al. 2016

JoVE

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Here we describe a protocol that can be used to study the biophysical microenvironment related to increased thickness and stiffness of the basement membrane (BM) during age-related pathologies and metabolic disorders (e.g. cancer, diabetes, microvascular disease, retinopathy, nephropathy and neuropathy). The premise of the model is non-enzymatic crosslinking of reconstituted BM (rBM) matrix by treatment with glycolaldehyde (GLA) to promote advanced glycation endproduct (AGE) generation via the Maillard reaction. Examples of laboratory techniques that can be used to confirm AGE generation, non-enzymatic crosslinking and increased stiffness in GLA treated rBM are outlined. These include preparation of native rBM (treated with phosphate-buffered saline, PBS) and stiff rBM (treated with GLA) for determination of: its AGE content by photometric analysis and immunofluorescent microscopy, its non-enzymatic crosslinking by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) as well as confocal microscopy, and its increased stiffness using rheometry. The procedure described here can be used to increase the rigidity (elastic moduli, E) of rBM up to 3.2-fold, consistent with measurements made in healthy versus diseased human prostate tissue. To recreate the biophysical microenvironment associated with the aging and diseased prostate gland three prostate cell types were introduced on to native rBM and stiff rBM: RWPE-1, prostate epithelial cells (PECs) derived from a normal prostate gland; BPH-1, PECs derived from a prostate gland affected by benign prostatic hyperplasia (BPH); and PC3, metastatic cells derived from a secondary bone tumor originating from prostate cancer. Multiple parameters can be measured, including the size, shape and invasive characteristics of the 3D glandular acini formed by RWPE-1 and BPH-1 on native versus stiff rBM, and average cell length, migratory velocity and persistence of cell movement of 3D spheroids formed by PC3 cells under the same conditions. Cell signaling pathways and the subcellular localization of proteins can also be assessed.

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Engineering Cell‐Derived Matrices: From 3D Models to Advanced Personalized Therapies

Rubí-Sans

Castaño

Cano

et al. 2020

Adv Funct Materials

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Regenerative medicine and disease models have evolved in recent years from two to three dimensions, providing in vitro constructs that are more similar to in vivo tissues. By mimicking native tissues, cell-derived matrices (CDMs) have emerged as new modifiable extracellular matrices for a variety of tissues, allowing researchers to study basic cellular processes in tissue-like structures, test tissue regeneration approaches, and model disease development. In this review, different fabrication techniques and characterization methods of CDMs are presented and examples of their application in cell behavior studies, tissue regeneration, and disease models are provided. In addition, future guidelines and perspectives in the field of CDMs are discussed.

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Tumor-associated Endo180 requires stromal-derived LOX to promote metastatic prostate cancer cell migration on human ECM surfaces

Cited by 19 publications

References 61 publications

Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

How to Study Basement Membrane Stiffness as a Biophysical Trigger in Prostate Cancer and Other Age-related Pathologies or Metabolic Diseases

Engineering Cell‐Derived Matrices: From 3D Models to Advanced Personalized Therapies

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