Distinctive Features of Advancing Breast Cancer Cells and Interactions with Surrounding Stroma Observed Under the Scanning Electron Microscope

Jaafar, Hasnan; Sharif, Sharifah Emilia Tuan; Murtey, Mogana Das

doi:10.7314/apjcp.2012.13.4.1305

Cited by 8 publications

(6 citation statements)

References 31 publications

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“…A drastic decrease in MT1-MMP was observed in prostate cancer cells seeded upon lumican which was no longer detected in cellular projections. Lamellipodia and invadopodia are formed at the leading edge of migrating cells, such as breast cancer cells which present both lamellipodia and invadopodia, and jointly enable their migration and invasion [60, 62]. Our results further revealed that lumican also induces a loss of invadopodia formation in prostate cancer cells.…”

Section: Discussionsupporting

confidence: 61%

Lumican expression, localization and antitumor activity in prostate cancer

Coulson‐Thomas

Coulson-Thomas

Gesteira

et al. 2013

Experimental Cell Research

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The stromal reaction surrounding tumors leads to the formation of a tumor-specific microenvironment, which may play either a restrictive role or a supportive role in the growth and progression of the tumors. Lumican, a small leucine-rich proteoglycan (SLRP) of the extracellular matrix (ECM), regulates collagen fibrillogenesis. Recently, lumican has also been shown to regulate cell behavior during embryonic development, tissue repair and tumor progression. The role of lumican in cancer varies according to the type of tumor. In this study we analyze the role of lumican in the pathogenesis of prostate cancer both in vivo and in vitro. Overall lumican up-regulation was observed in the primary tumors analyzed through both real-time PCR and immunostaining. The increase in lumican expression was observed in the reactive stroma surrounding prostate primary tumors with fibrotic deposition surrounding the acinar glands. In vitro analysis demonstrated that lumican inhibited both the migration and invasion of metastatic prostate cancer cells isolated from lymph node, bone and brain. Moreover, prostate cancer cells seeded on lumican presented a decrease in the formation of cellular projections, lamellipodia detected by a decreased rearrangement in ZO-1, keratin 8/18, integrin β1 and MT1-MMP, and invadopodia detected by disruption of α-smooth muscle actin, cortactin and N-WASP. Moreover, a significant increase in prostate cancer cell invasion was observed through the peritoneum of lumican knockout mice, further demonstrating the restrictive role lumican present in the ECM has on prostate cancer invasion. In conclusion, lumican present in the reactive stroma surrounding prostate primary tumors plays a restrictive role on cancer progression, and we therefore postulate that lumican could be a valuable marker in prostate cancer staging.

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Section: Discussionsupporting

confidence: 61%

Lumican expression, localization and antitumor activity in prostate cancer

Coulson‐Thomas

Coulson-Thomas

Gesteira

et al. 2013

Experimental Cell Research

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“…Cancer cell invasion and intravasation are the initial steps of metastasis during tumor progression [1,2,3]. Extracellular matrix (ECM), the main component of connective tissues, is a physical scaffold, which must adapt to deformations caused by internal and external mechanical stresses.…”

Section: Introductionmentioning

confidence: 99%

Collagen Fiber Array of Peritumoral Stroma Influences Epithelial-to-Mesenchymal Transition and Invasive Potential of Mammary Cancer Cells

Franchi

Masola

Bellin

et al. 2019

JCM

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: Interactions of cancer cells with matrix macromolecules of the surrounding tumor stroma are critical to mediate invasion and metastasis. In this study, we reproduced the collagen mechanical barriers in vitro (i.e., basement membrane, lamina propria under basement membrane, and deeper bundled collagen fibers with different array). These were used in 3D cell cultures to define their effects on morphology and behavior of breast cancer cells with different metastatic potential (MCF-7 and MDA-MB-231) using scanning electron microscope (SEM). We demonstrated that breast cancer cells cultured in 2D and 3D cultures on different collagen substrates show different morphologies: i) a globular/spherical shape, ii) a flattened polygonal shape, and iii) elongated/fusiform and spindle-like shapes. The distribution of different cell shapes changed with the distinct collagen fiber/fibril physical array and size. Dense collagen fibers, parallel to the culture plane, do not allow the invasion of MCF-7 and MDA-MB-231 cells, which, however, show increases of microvilli and microvesicles, respectively. These novel data highlight the regulatory role of different fibrillar collagen arrays in modifying breast cancer cell shape, inducing epithelial-to-mesenchymal transition, changing matrix composition and modulating the production of extracellular vesicles. Further investigation utilizing this in vitro model will help to demonstrate the biological roles of matrix macromolecules in cancer cell invasion in vivo.

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“…Although the rat model of MNU-induced mammary tumors is one of the most frequently used in breast cancer research, little is known about the ultrastructure of these cancer cells (Faustino-Rocha et al, 2015 a ). Once cells undergo transformations during the process of carcinogenesis (Jaafar et al, 2012), we consider it important to analyze their ultrastructure in order to better understand and justify the observable macroscopic alterations. Thus, TEM was carried out in three samples from MNU-induced mammary tumors in female Sprague-Dawley rats.…”

Section: Discussionmentioning

confidence: 99%

Electron Microscopy Findings inN-Methyl-N-Nitrosourea-Induced Mammary Tumors

et al. 2016

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Although the rat model of mammary tumors chemically induced by N-methyl-N-nitrosourea (MNU) has been frequently used by several research teams, there is a lack of ultrastructural studies in this field. The main aim of this work was to perform an ultrastructural characterization of MNU-induced mammary tumors in female rats. Some alterations previously reported in human mammary tumors, such as nucleus size and shape, accumulation of heterochromatin in the perinuclear region, and interdigitating cytoplasmic processes between cancer cells were also observed in MNU-induced mammary tumors. Although a low number of samples were analyzed by transmission electron microscopy in the present study, we consider that it may contribute to a better understanding of MNU-induced mammary carcinogenesis in a rat model. The ultrastructural characteristics of the two most frequently diagnosed mammary carcinomas described in the present work can be useful to differentiate them from other histological patterns. In addition, the loss of cytoplasm in neoplastic cells and formation of vacuoles were described.

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Distinctive Features of Advancing Breast Cancer Cells and Interactions with Surrounding Stroma Observed Under the Scanning Electron Microscope

Cited by 8 publications

References 31 publications

Lumican expression, localization and antitumor activity in prostate cancer

Lumican expression, localization and antitumor activity in prostate cancer

Collagen Fiber Array of Peritumoral Stroma Influences Epithelial-to-Mesenchymal Transition and Invasive Potential of Mammary Cancer Cells

Electron Microscopy Findings inN-Methyl-N-Nitrosourea-Induced Mammary Tumors

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