Invasive cancers are not necessarily from preformed <i>in situ</i> tumours — an alternative way of carcinogenesis from misplaced stem cells

Wang, Rui‐An; Li, Zengshan; Zhang, Huizhong; Zheng, Ping-Ju; Li, Qin-Long; Shi, Jing; Qu, Yan; Ye, Jing; Wang, Jingbo; Guo, Ying; Huang, Xiaofeng; Yu, Yinhua

doi:10.1111/jcmm.12078

Cited by 31 publications

(33 citation statements)

References 26 publications

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“…Without question the CSC theory opened a new chapter in cancer research but serious concerns have been raised questioning its value to explain the vast majority of cancers especially that it "is likely that we are still evaluating the main population of tumour cells, which are not cancer stem cells, and are thus probably wasting time and losing essential treatment information" and that it is "unlikely that gene expression profiles obtained using the currently available methods reflect those of the tumour stem cell population, which forms only 0.1-2% of the whole tissue sample" [88]. Later, it was also proposed, that "misplaced epithelial stem cell which lands to the wrong location of stromal connective tissue by accident" would result in carcinogenesis [40].…”

Section: Stem Cell Theorymentioning

confidence: 99%

Prelude and premise to the special issue: disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer”

Brücher

Jamall

2019

4open

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The vast majority of anticancer strategies are symptomatic but in order to achieve some tangible progress, we need to identify the cause(s) of the majority of cancers. There is a kind of zeitgeist that findings in genetics, namely somatic mutations, are reflexively viewed as being causative for carcinogenesis, although some 80% of all cancers are presently termed “sporadic” (i.e., with no proven cause). The observation that one inch of cancerous liver tissue can have more than 100 000 000 mutations and an identical mutation can result in different phenotypes, depending on the environment surrounding that mutation, makes it very unlikely that mutations by themselves are causative of most cancers. 4open debuts its Special Issue series with papers that provide strong evidence that carcinogenesis consists of a 6-step sequence (1) a pathogenic stimulus followed by (2) chronic inflammation from which develops (3) fibrosis with associated remodeling of the extracellular microenvironment, and from these changes a (4) precancerous niche (PCN), a product of fibrosis with remodeling by persistent inflammation develops which triggers the deployment of (5) a chronic stress escape strategy and when this fails to be resolved it results in (6) the normal cell to cancerous cell transition. This Special Issue contains separate papers discussing undervalued ubiquitous proteins, chronic inflammation, eicosanoids, microbiome and morbid obesity, PCN, cell transition, followed by altered signaling induced by Metformin, NF-κB signaling and crosstalk during carcinogenesis, and a brief synopsis. In essence, the available evidence, both in vitro and in vivo, lends credence to the proposition that the majority of cancers occur from a disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer”.

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Section: Stem Cell Theorymentioning

confidence: 99%

Prelude and premise to the special issue: disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer”

Brücher

Jamall

2019

4open

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“…PRB-H tumors recapitulate luminal B molecular subtypes (low total PR levels, high ki67 levels, are resistant to antiprogestin therapy and may respond to progestin therapy). Invasive carcinomas may arise from DCIS (Cowell et al 2013) or directly from mammary stem cells (Wang et al 2013). DCIS, ductal carcinoma in situ; PR, progesterone receptor; PRA-H, higher levels of PRA than PRB; PRB-H, higher levels of PRB than PRA.…”

Section: Clinical Trialsmentioning

confidence: 99%

Biological and clinical impact of imbalanced progesterone receptor isoform ratios in breast cancer

Lamb¹,

Fabris²,

Jacobsen

et al. 2018

Endocrine-Related Cancer

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There is a consensus that progestins and thus their cognate receptor molecules, the progesterone receptors (PR), are essential in the development of the adult mammary gland and regulators of proliferation and lactation. However, a role for natural progestins in breast carcinogenesis remains poorly understood. A hint to that possible role came from studies in which the synthetic progestin medroxyprogesterone acetate was associated with an increased breast cancer risk in women under hormone replacement therapy. However, progestins have been also used for breast cancer treatment and to inhibit the growth of several experimental breast cancer models. More recently, PR have been shown to be regulators of estrogen receptor signaling. With all this information, the question is how can we target PR, and if so, which patients may benefit from such an approach? PR are not single unique molecules. Two main PR isoforms have been characterized, PRA and PRB, that exert different functions and the relative abundance of one isoform respect to the other determines the response of PR agonists and antagonists. Immunohistochemistry with standard antibodies against PR do not discriminate between isoforms. In this review, we summarize the current knowledge on the expression of both PR isoforms in mammary glands, in experimental models of breast cancer and in breast cancer patients, to better understand how the PRA/PRB ratio can be exploited therapeutically to design personalized therapeutic strategies.

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“…Several theories have been proposed for the origin of BCSCs, including improper regulation or mutations that may lead to the transformation of dormant normal stem cells into BCSCs (7), de novo misplacement of somatic stem cells (8), and intratumoral lineages differentiated from common progenitor cells (9). Common BCSC characteristics have been reported in several studies.…”

Section: The Origin and Characteristics Of Bcscsmentioning

confidence: 99%

Are breast cancer stem cells the key to resolving clinical issues in breast cancer therapy?

Shima¹,

Yamada²,

Ishikawa³

et al. 2017

Gland Surg.

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Despite the dramatic advances in breast cancer treatment over the past two decades, it is still the most common malignancies in women. One of the reasons patients succumb to breast cancer is treatment resistance leading to metastasis and recurrence. Recently, cancer stem cells (CSCs) have been suggested as a cause of metastasis and recurrence in several cancers because of their unique characteristics, including self-renewal, pluripotency, and high proliferative ability. Increasing evidence has implicated breast cancer stem cells (BCSCs) as essential for tumor development, progression, recurrence, and treatment resistance.

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Invasive cancers are not necessarily from preformed in situ tumours — an alternative way of carcinogenesis from misplaced stem cells

Cited by 31 publications

References 26 publications

Prelude and premise to the special issue: disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer”

Prelude and premise to the special issue: disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer”

Biological and clinical impact of imbalanced progesterone receptor isoform ratios in breast cancer

Are breast cancer stem cells the key to resolving clinical issues in breast cancer therapy?

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