Tube-Like Structures with Co-Expression of D2-40 and CD34: Newly Formed Vasculatures?

Jiang, Bin; Mason, Jeffrey T.; Jewett, Anahid; Cho, William C.; Man, Yan‐gao

doi:10.7150/ijbs.5147

Cited by 7 publications

(4 citation statements)

References 64 publications

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“…More importantly, our studies have detected nearly identical focal capsule disruptions, lymphocyte infiltration, budding cell clusters, and the formation of TLCs in normal colorectal epithelial structures both distant from, and adjacent to, malignant lesions 65-66. Compared to their morphologically similar counterparts, node-positive CRC have the following unique alterations:…”

Section: Introductionsupporting

confidence: 53%

See 1 more Smart Citation

Cell Budding from Normal Appearing Epithelia: A Predictor of Colorectal Cancer Metastasis?

Jiang¹,

Mason²,

Jewett³

et al. 2013

Int. J. Biol. Sci.

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Background: Colorectal carcinogenesis is believed to be a multi-stage process that originates with a localized adenoma, which linearly progresses to an intra-mucosal carcinoma, to an invasive lesion, and finally to metastatic cancer. This progression model is supported by tissue culture and animal model studies, but it is difficult to reconcile with several well-established observations, principally among these are that up to 25% of early stage (Stage I/II), node-negative colorectal cancer (CRC) develop distant metastasis, and that circulating CRC cells are undetectable in peripheral blood samples of up to 50% of patients with confirmed metastasis, but more than 30% of patients with no detectable metastasis exhibit such cells. The mechanism responsible for this diverse behavior is unknown, and there are no effective means to identify patients with pending, or who are at high risk for, developing metastatic CRC.Novel findings: Our previous studies of human breast and prostate cancer have shown that cancer invasion arises from the convergence of a tissue injury, the innate immune response to that injury, and the presence of tumor stem cells within tumor capsules at the site of the injury. Focal degeneration of a capsule due to age or disease attracts lymphocyte infiltration that degrades the degenerating capsules resulting in the formation of a focal disruption in the capsule, which selectively favors proliferating or “budding” of the underlying tumor stem cells. Our recent studies suggest that lymphocyte infiltration also triggers metastasis by disrupting the intercellular junctions and surface adhesion molecules within the proliferating cell buds causing their dissociation. Then, lymphocytes and tumor cells are conjoined through membrane fusion to form tumor-lymphocyte chimeras (TLCs) that allows the tumor stem cell to avail itself of the lymphocyte's natural ability to migrate and breach cell barriers in order to intravasate and to travel to distant organs. Our most recent studies of human CRC have detected nearly identical focal capsule disruptions, lymphocyte infiltration, budding cells, and the formation of TLCs. Our studies have further shown that age- and type-matched node-positive and -negative CRC have a significantly different morphological and immunohistochemical profile and that the majority of lymphatic ducts with disseminated cells are located within the mucosa adjacent to morphologically normal appearing epithelial structures that express a stem cell-related marker.New hypothesis: Based on these findings and the growth patterns of budding cells revealed by double immunohistochemistry, we further hypothesize that metastatic spread is an early event of carcinogenesis and that budding cells overlying focal capsule disruptions represent invasion- and metastasis-initiating cells that follow one of four pathways to progress: (1) to undergo extensive in situ proliferation leading to the formation of tumor nests that subsequently invade the submucosa, (2) to migrate with associated lymphocytes functioning a...

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Section: Introductionsupporting

confidence: 53%

“…In summary, this is a hypothesis paper, based on our previously published experimental data of studies in human breast and prostate tumors 26-37 and recent unpublished findings in human CRC 65,66. Our current study is the expansion of our previous studies with same concept and technical approaches.…”

Section: Implications Of Our Hypothesismentioning

confidence: 89%

Cell Budding from Normal Appearing Epithelia: A Predictor of Colorectal Cancer Metastasis?

Jiang¹,

Mason²,

Jewett³

et al. 2013

Int. J. Biol. Sci.

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“…Interactions between CSCs and tumor endothelial cells also play a major role in sequestering the angiogenic process as documented in brain cancer where Nestin + /CD133 + CSCs are located in direct proximity of endothelial cells. Considering the close association between CSCs and tumor endothelial cells, it has been proposed that newly formed vasculature within a growing tumor can be derived from the differentiation of CSCs implicating its multilineage differentiation capabilities …”

Section: Factors Governing Solid Tumor Heterogeneity and Csc Plasticitymentioning

confidence: 99%

Tumor heterogeneity and cancer stem cell paradigm: Updates in concept, controversies and clinical relevance

Singh

Arya

Maheshwari

et al. 2014

Intl Journal of Cancer

123

112

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Although tumor heterogeneity is widely accepted, the existence of cancer stem cells (CSCs) and their proposed role in tumor maintenance has always been challenged and remains a matter of debate. Recently, a path-breaking chapter was added to this saga when three independent groups reported the in vivo existence of CSCs in brain, skin and intestinal tumors using lineage-tracing and thus strengthens the CSC concept; even though certain fundamental caveats are always associated with lineage-tracing approach. In principle, the CSC hypothesis proposes that similar to normal stem cells, CSCs maintain self renewal and multilineage differentiation property and are found at the central echelon of cellular hierarchy present within tumors. However, these cells differ from their normal counterpart by maintaining their malignant potential, alteration of genomic integrity, epigenetic identity and the expression of specific surface protein profiles. As CSCs are highly resistant to chemotherapeutics, they are thought to be a crucial factor involved in tumor relapse and superficially appear as the ultimate therapeutic target. However, even that is not the end; further complication is attributed by reports of bidirectional regeneration mechanism for CSCs, one from their self-renewal capability and another from the recently proposed concept of dynamic equilibrium between CSCs and non-CSCs via their interconversion. This phenomenon has currently added a new layer of complexity in understanding the biology of tumor heterogeneity. In-spite of its associated controversies, this area has rapidly emerged as the center of attention for researchers and clinicians, because of the conceptual framework it provides towards devising new therapies.

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“…MVD is a possible predictor of LNM in patients with CRC 31 . Another study showed that tube-like structures co-expressing D240 and CD34 were often observed at the junctions between preinvasive and invasive CRC 32 . Lymphatic vessels (LV and D240 positive) have been found even in the mucosa of in situ CRC, indicating the presence of a low tumor burden in regional LNs 33 .…”

Section: Discussionmentioning

confidence: 99%

Finding the minimum number of retrieved lymph nodes in Node-negative colorectal cancer using Real-world Data and the SEER database

Qiao,

Zhu,

Han

et al. 2023

International Journal of Surgery

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Background: Current clinical guidelines recommend the removal of at least 12 lymph nodes (LNs) in resectable colorectal cancer (CRC). With advancements in lymphadenectomy technologies, the number of retrieved lymph nodes (rLNs) has markedly increased. This study aimed to investigate the lowest number of rLNs in node-negative patients. Materials and Methods: A total of 1103 N0 and 208 N1a stage patients were enrolled in our cohort, while 8503 N0 and 1276 N1a patients from the Surveillance, Epidemiology, and End Results CRC database were included. Propensity score matching and multivariate Cox regression analyses were performed to mitigate the influence of selection bias and control for potential confounding variables. Results: The median number of rLNs in N0 patients increased from 13.5 (interquartile range [IQR]: 9-18) in 2013 to 17 (IQR: 15-20) in 2019. The restrictive cubic spline illustrated a nonlinear relationship between rLNs and prognosis (nonlinearity, P=0.009), with a threshold (N=16) influencing clinical outcomes. Patients at either N0 or N1a stage with sufficient rLNs (≥ 16) demonstrated superior prognoses to those with a limited rLNs (<16). After adjusting for clinical confounders, similar prognoses were observed in N0 limited and N1a adequate populations. Furthermore, Kaplan-Meier curves revealed N0 limited patients who received chemotherapy exhibited better outcomes than those who did not. Conclusions: Among patients with node-negative CRC, it is crucial to remove 16 or more LNs effectively. Fewer than 16 rLNs should be regarded as an independent risk factor, implying the need for adjuvant chemotherapy.

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Tube-Like Structures with Co-Expression of D2-40 and CD34: Newly Formed Vasculatures?

Cited by 7 publications

References 64 publications

Cell Budding from Normal Appearing Epithelia: A Predictor of Colorectal Cancer Metastasis?

Cell Budding from Normal Appearing Epithelia: A Predictor of Colorectal Cancer Metastasis?

Tumor heterogeneity and cancer stem cell paradigm: Updates in concept, controversies and clinical relevance

Finding the minimum number of retrieved lymph nodes in Node-negative colorectal cancer using Real-world Data and the SEER database

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