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Journal of Cancer Research and Clinical Oncology

Erschienen in:

23.11.2018 | Original Article – Cancer Research

Spatiotemporal characteristics of fibroblasts-dependent cancer cell invasion

verfasst von: Tomoyuki Miyashita, Tomokazu Omori, Hiroshi Nakamura, Masato Sugano, Shinya Neri, Satoshi Fujii, Hiroko Hashimoto, Masahiro Tsuboi, Atsushi Ochiai, Genichiro Ishii

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2019

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Abstract

Purpose

Cancer cells can invade the surrounding stroma with the aid of fibroblasts (fibroblasts-dependent invasion). The aim of this study was to explore the spatiotemporal characteristics of fibroblast-dependent invasion of cancer cells.

Methods

We performed an in vitro three-dimensional collagen invasion assay using Fluorescent Ubiquitination-based Cell Cycle indicator (Fucci)-labeled A431 carcinoma cells co-cultured with fibroblasts. We used time-lapse imaging to analyze the total cell number, frequencies of small cancer cell nests and S/G2/M phase of A431 cells in the invasion area. We compared the frequencies of small cancer cell nests and geminin (+) cancer cells within fibroblast-rich areas and fibroblast-poor areas in surgically resected human invasive squamous cell carcinoma tissue.

Results

The total invasion number of A431 cells was significantly higher when cultured with fibroblasts than without. The formation of small cancer cell nests was observed within the invasion area only in the presence of fibroblasts. The frequency of S/G2/M phase cells was significantly higher in A431 cells when cultured with fibroblasts than without. Immunohistochemical analysis of surgically resected human invasive squamous cell carcinoma tissue revealed that the frequencies of small cancer cell nests and geminin-positive cancer cells were significantly higher in fibroblast-rich areas compared to those in fibroblast-poor areas within the same tumor region.

Conclusion

Our current study clearly showed that fibroblast-dependent cancer cell invasion was characterized by the progression in cell cycle and formation of small cancer cell nests.

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Christiansen JJ, Rajasekaran AK (2006) Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res 66:8319–8326CrossRefPubMed

Clark AG, Vignjevic DM (2015) Modes of cancer cell invasion and the role of the microenvironment. Curr Opin Cell Biol 36:13–22CrossRefPubMed

Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174CrossRefPubMed

Friedl P, Alexander S (2011) Cancer invasion and the microenvironment: plasticity and reciprocity. Cell 147:992–1009CrossRefPubMed

Friedl P, Wolf K (2003) Tumour-cell invasion and migration diversity and escape mechanisms. Nat Rev Cancer 3:362–374CrossRefPubMed

Friedl P, Wolf K (2009) Proteolytic interstitial cell migration: a five-step process. Cancer Metastasis Rev 28:129–135CrossRefPubMed

Friedl P, Locker J, Sahai E, Segall JE (2012) Classifying collective cancer cell invasion. Nat Cell Biol 14:777–783CrossRefPubMed

Funai K, Yokose T, Ishii G, Araki K, Yoshida J, Nishimura M, Nagai K, Nishiwaki Y, Ochiai A (2003) Clinicopathologic characteristics of peripheral squamous cell carcinoma of the lung. Am J Surg Pathol 27:978–984CrossRefPubMed

Gaggioli C, Hooper S, Hidalgo-Carcedo C, Grosse R, Marshall JF, Harrington K, Sahai E (2007) Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol 9:1392–1400CrossRefPubMed

Gao Y, Wang Z, Hao Q, Li W, Xu Y, Zhang J, Zhang W, Wang S, Liu S, Li M, Xue X, Zhang W, Zhang C, Zhang Y (2017) Loss of ERalpha induces amoeboid-like migration of breast cancer cells by downregulating vinculin. Nat Commun 8:14483CrossRefPubMedPubMedCentral

Ishii G, Ochiai A, Neri S (2016) Phenotypic and functional heterogeneity of cancer-associated fibroblast within the tumor microenvironment. Adv Drug Deliv Rev 99:186–196CrossRefPubMed

Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6:392–401CrossRefPubMed

Khalil AA, Friedl P (2010) Determinants of leader cells in collective cell migration. Integr Biol (Camb) 2:568–574CrossRef

Konen J, Summerbell E, Dwivedi B, Galior K, Hou Y, Rusnak L, Chen A, Saltz J, Zhou W, Boise LH, Vertino P, Cooper L, Salaita K, Kowalski J, Marcus AI (2017) Image-guided genomics of phenotypically heterogeneous populations reveals vascular signalling during symbiotic collective cancer invasion. Nat Commun 8:15078CrossRefPubMedPubMedCentral

Labernadie A, Kato T, Brugues A, Serra-Picamal X, Derzsi S, Arwert E, Weston A, Gonzalez-Tarrago V, Elosegui-Artola A, Albertazzi L, Alcaraz J, Roca-Cusachs P, Sahai E, Trepat X (2017) A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion. Nat Cell Biol 19:224–237CrossRefPubMedPubMedCentral

Lammermann T, Sixt M (2009) Mechanical modes of ‘amoeboid’ cell migration. Curr Opin Cell Biol 21:636–644CrossRefPubMed

Madsen CD, Sahai E (2010) Cancer dissemination–lessons from leukocytes. Dev Cell 19:13–26CrossRefPubMed

Miyashita T, Higuchi Y, Kojima M, Ochiai A, Ishii G (2017) Single cell time-lapse analysis reveals that podoplanin enhances cell survival and colony formation capacity of squamous cell carcinoma cells. Sci Rep 7:39971CrossRefPubMedPubMedCentral

Neri S, Ishii G, Hashimoto H, Kuwata T, Nagai K, Date H, Ochiai A (2015) Podoplanin-expressing cancer-associated fibroblasts lead and enhance the local invasion of cancer cells in lung adenocarcinoma. Int J Cancer 137:784–796CrossRefPubMed

Neri S, Hashimoto H, Kii H, Watanabe H, Masutomi K, Kuwata T, Date H, Tsuboi M, Goto K, Ochiai A, Ishii G (2016) Cancer cell invasion driven by extracellular matrix remodeling is dependent on the properties of cancer-associated fibroblasts. J Cancer Res Clin Oncol 142:437–446CrossRefPubMed

Neri S, Miyashita T, Hashimoto H, Suda Y, Ishibashi M, Kii H, Watanabe H, Kuwata T, Tsuboi M, Goto K, Menju T, Sonobe M, Date H, Ochiai A, Ishii G (2017) Fibroblast-led cancer cell invasion is activated by epithelial-mesenchymal transition through platelet-derived growth factor BB secretion of lung adenocarcinoma. Cancer Lett 395:20–30CrossRefPubMed

Sahai E (2007) Illuminating the metastatic process. Nat Rev Cancer 7:737–749CrossRefPubMed

Sakaue-Sawano A, Kobayashi T, Ohtawa K, Miyawaki A (2011) Drug-induced cell cycle modulation leading to cell-cycle arrest, nuclear mis-segregation, or endoreplication. BMC Cell Biol 12:2CrossRefPubMedPubMedCentral

Sanz-Moreno V, Marshall CJ (2010) The plasticity of cytoskeletal dynamics underlying neoplastic cell migration. Curr Opin Cell Biol 22:690–696CrossRefPubMed

Sanz-Moreno V, Gadea G, Ahn J, Paterson H, Marra P, Pinner S, Sahai E, Marshall CJ (2008) Rac activation and inactivation control plasticity of tumor cell movement. Cell 135:510–523CrossRefPubMed

Schroeder A, Heller DA, Winslow MM, Dahlman JE, Pratt GW, Langer R, Jacks T, Anderson DG (2011) Treating metastatic cancer with nanotechnology. Nat Rev Cancer 12:39–50CrossRefPubMed

Skhinas JN, Cox TR (2017) The interplay between extracellular matrix remodelling and kinase signalling in cancer progression and metastasis. Cell Adh Migr 1–9

Sleeman JP, Thiery JP: SnapShot (2011) The epithelial-mesenchymal transition. Cell 145:162 e1

Tsuji T, Ibaragi S, Hu GF (2009) Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res 69:7135–7139CrossRefPubMedPubMedCentral

Wolf K, Friedl P (2011) Extracellular matrix determinants of proteolytic and non-proteolytic cell migration. Trends Cell Biol 21:736–744CrossRefPubMed

Wolf K, Muller R, Borgmann S, Brocker EB, Friedl P (2003) Amoeboid shape change and contact guidance: T-lymphocyte crawling through fibrillar collagen is independent of matrix remodeling by MMPs and other proteases. Blood 102:3262–3269CrossRefPubMed

Wolf K, Wu YI, Liu Y, Geiger J, Tam E, Overall C, Stack MS, Friedl P (2007) Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nat Cell Biol 9:893–904CrossRefPubMed

Titel: Spatiotemporal characteristics of fibroblasts-dependent cancer cell invasion
verfasst von: Tomoyuki Miyashita
Tomokazu Omori
Hiroshi Nakamura
Masato Sugano
Shinya Neri
Satoshi Fujii
Hiroko Hashimoto
Masahiro Tsuboi
Atsushi Ochiai
Genichiro Ishii
Publikationsdatum: 23.11.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-018-2798-y

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Spatiotemporal characteristics of fibroblasts-dependent cancer cell invasion